SHR902275 is a potent, selective, and orally active RAF inhibitor targeting RAS mutant cancers. SHR902275 has IC50s of 1.6 nM, 10 nM, and 5.7 nM for cRAF, bRAFwt, and bRAFV600E, respectively. SHR902275 shows cell growth inhibition with GI50s of 1.5 and 0.17 nM, 0.4 nM and 0.32 nM for H358, A375, Calu6, and SK-MEL2 cells respectively[1].
IC50 & Target[1]
c-Raf
1.6 nM (IC50)
BRafV600E
5.7 nM (IC50)
BRAFWT
10 nM (IC50)
分子量
512.48
Formula
C26H23F3N4O4
CAS 号
2695506-82-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Zhao P, et al. Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers. Eur J Med Chem. 2022;228:114040.
SHR902275 is a potent, selective, and orally active RAF inhibitor targeting RAS mutant cancers. SHR902275 has IC50s of 1.6 nM, 10 nM, and 5.7 nM for cRAF, bRAFwt, and bRAFV600E, respectively. SHR902275 shows cell growth inhibition with GI50s of 1.5 and 0.17 nM, 0.4 nM and 0.32 nM for H358, A375, Calu6, and SK-MEL2 cells respectively[1].
IC50 & Target[1]
c-Raf
1.6 nM (IC50)
BRafV600E
5.7 nM (IC50)
BRAFWT
10 nM (IC50)
分子量
512.48
Formula
C26H23F3N4O4
CAS 号
2695506-82-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Zhao P, et al. Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers. Eur J Med Chem. 2022;228:114040.
SHR902275 is a potent, selective, and orally active RAF inhibitor targeting RAS mutant cancers. SHR902275 has IC50s of 1.6 nM, 10 nM, and 5.7 nM for cRAF, bRAFwt, and bRAFV600E, respectively. SHR902275 shows cell growth inhibition with GI50s of 1.5 and 0.17 nM, 0.4 nM and 0.32 nM for H358, A375, Calu6, and SK-MEL2 cells respectively[1].
IC50 & Target[1]
c-Raf
1.6 nM (IC50)
BRafV600E
5.7 nM (IC50)
BRAFWT
10 nM (IC50)
分子量
512.48
Formula
C26H23F3N4O4
CAS 号
2695506-82-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Zhao P, et al. Discovery of spiro amide SHR902275: A potent, selective, and efficacious RAF inhibitor targeting RAS mutant cancers. Eur J Med Chem. 2022;228:114040.
Pyrotinib dimaleate (SHR-1258 dimaleate) is a potent and selective EGFR/HER2 dual inhibitor with IC50s of 13 and 38 nM, respectively[1].
IC50 & Target[1]
HER2
38 nM (IC50)
EGFR
13 nM (IC50)
体外研究 (In Vitro)
Pyrotinib dimaleate has high potency in HER2-dependent cell lines (BT474, SK-OV-3), while showing much weaker inhibition in the HER2 negative cell line (MDA-MB-231). Pyrotinib dimaleate inhibits BT474 and SK-OV-3 cells with IC50s of 5.1 and 43 nM, respectively. Pyrotinib dimaleate displays high selectivity as HKI-272 when tested in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and C-Met (c-Src with an IC50 of 790 nM, and others >3000 nM)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Pyrotinib dimaleate has acceptable bioavailability of 20.6%, 43.5% and 13.5% in nude mice, rats and dogs, respectively. Pyrotinib dimaleate has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects (oral; t1/2=15 h) with a much longer half life than that of preclinical animal species such as mouse (i.v.; t1/2=1.56 h; i.g.; t1/2=2.52 h) and rat (i.v.; t1/2=4.42 h; i.g.; t1/2=3.38 h)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
815.22
Formula
C40H39ClN6O11
CAS 号
1397922-61-0
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Li X, et al. Discovery and development of Pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Jan 21. pii: S0928-0987(17)30043-X.
Cell Assay [1]
Cancer cells (A431, SK-BR-3 and NCI-N87) are treated at a suitable concentration of Pyrotinib for 72 hours. Cell proliferation is determined by a sulforhodamine B (SRB) method. The IC50 values are calculated by the data of inhibition rates of serial concentrations of Pyrotinib dimaleate[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Rats[1] Sprague Dawley (SD) rats (200-250g, 3 males and 3 females) are used .Test compounds (include Pyrotinib dimaleate) are administrated in both intravenous ( i.v. ; 3 mg/kg) and intragastric ( i.g. ;3 mg/kg) for rats to obtain their bioavailability. Plasma samples of nude mice is collected at pre-dose and 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h after the IV administration [1]. Mice[1]: In vivo efficacy studies are performed on BALB/Ca-nude mice (6 to 7 weeks, female) from SLAC. Nude mice are hypodermic inoculated BT-474 human breast cancer cell or SK-OV-3 ovarian cancer cell. After tumor grows to 150-250 mm3, mice are randomly divided into groups and dosed with Pyrotinib (2.5, 5, 10, 20 mg/kg) once daily. The volume of tumors and the weight of the mice are measured and recorded for 2-3 times per weeks[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Li X, et al. Discovery and development of Pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Jan 21. pii: S0928-0987(17)30043-X.
Fluzoparib (SHR3162) is a potent and orally active PARP1 inhibitor (IC50=1.46±0.72 nM, a cell‐free enzymatic assay) with superior antitumor activity. Fluzoparib selectively inhibits the proliferation of homologous recombination repair (HR)‐deficient cells, and sensitizes both HR‐deficient and HR‐proficient cells to cytotoxic agents. Fluzoparib exhibits good pharmacokinetic properties in vivo and can be used for BRCA1/2-mutant relapsed ovarian cancer research[1].
IC50 & Target[1]
PARP-1
1.46±0.72 nM (IC50)
体外研究 (In Vitro)
Fluzoparib (30 μM; 24 hour) increases the levels of γH2AX in a concentration‐dependent manner in both BRCA2‐deficient V‐C8 cells and BRCA1‐deficient MDA‐MB‐436 cells, but not in BRCA‐proficient V‐C8#13‐5 cells[1]. Fluzoparib (10 μM; 24 hour) increases levels of both pCDK1 and cyclin B, indicating activation of the G2/M checkpoint in MDA‐MB‐436 cells[1].Fluzoparib (10 μM; 72 hour) increases the processing of caspase‐3, ‐8, and ‐9 concentration‐dependently, it induces G2/M arrest and apoptosis in HR‐deficient MDA‐MB‐436 cells cells[1].Fluzoparib is preferentially efficacious against HR‐deficient cells, such as BRCA1‐deficient (UWB1.289), MDA‐MB‐436, BRCA2‐deficient (V‐C8), BRCA1‐deficientBRCA2‐mutated (MX‐1) and BRCA1 hypermethylated (OVCAR‐8) cells with IC50 values of 0.51 μM, 1.57 μM, 0.053 μM, 1.57 μM, and 1.43 μM, respectively. The IC50 values for HR‐proficient cells (V‐C8#13‐5 and UWB1.289 BRCA1) are both >10 μM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Fluzoparib (oral gavage; 0.3, 1, or 3 mg/kg; single dose) exhibits a good pharmacokinetic profile in Female Balb/cA nude mice (5‐6 weeks old) mice bearing MDA‐MB‐436. After a single oral dose, fluzoparib is rapidly absorbed and rapidly cleared from blood at all dose levels; plasma concentrations of fluzoparib quickly reaches maximum within 2 hours. In contrast, concentrations of fluzoparib in tumor remains at high levels even at 24 hours after dosing (57.9 ng/g , 39.3 ng/g, and 85.6 ng/g for doses of 0.3, 1, and 3 mg/kg, respectively)[1].Fluzoparib (oral gavage; 30 mg/kg; 21 days) apparently inhibits the growth of tumor with an inhibition rate of 59% (day 21) at 30 mg/kg, and it does not cause significant loss of body weight in Nude mice bearing MDA‐MB‐436 (BRCA1‐deficient) model[1].Fluzoparib (3mg/kg) combines with Cisplatin, Paclitaxel, or Apatinib (oral gavage; BID; 21 days) causes growth inhibition with rates of 61.4%, 55.3%, and 72.8%, respectively.Fluzoparib, Cisplatin, and Apatinib combination or Fluzoparib, Paclitaxel, and Apatinib combination can cause growth inhibition with rates of 84.9% and 75.6% (day 21), respectively in vivo.The 2‐drug combination of Fluzoparib with cisplatin and The 3‐drug Fluzoparib, Cisplatin, and Apatinib combination lead to loss of body weight, whereas no apparent toxicity was observed in other combinations[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
472.40
Formula
C22H16F4N6O2
CAS 号
1358715-18-0
中文名称
氟唑帕利
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 20.83 mg/mL (44.09 mM; ultrasonic and warming and heat to 60°C)
[1]. Lei Wang, et al. Pharmacologic characterization of fluzoparib, a novel poly(ADP-ribose) polymerase inhibitor undergoing clinical trials. Cancer Sci. 2019 Mar;110(3):1064-1075.
[2]. Huiping Li, et al. Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors. Chin J Cancer Res. 2020 Jun;32(3):370-382.
Pyrotinib (SHR-1258) is a potent and selective EGFR/HER2 dual inhibitor with IC50s of 13 and 38 nM, respectively[1].
IC50 & Target[1]
EGFR
13 nM (IC50)
HER2
38 nM (IC50)
体外研究 (In Vitro)
Pyrotinib has high potency in HER2-dependent cell lines (BT474, SK-OV-3), while showing much weaker inhibition in the HER2 negative cell line (MDA-MB-231). It inhibits BT474 and SK-OV-3Pyrotinib cells with IC50s of 5.1 and 43 nM, respectively. Pyrotinib displays high selectivity as HKI-272 when tested in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and C-Met (c-Src with an IC50 of 790 nM, and others over 3000 nM)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Pyrotinib has acceptable bioavailability of 20.6%, 43.5% and 13.5% in nude mice, rats and dogs, respectively. Pyrotinib has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects with a much longer half life than that of preclinical animal species such as mouse, rat and dog. The TGI % (tumor growth inhibition) of Pyrotinib on day 21 is 109%, 157%, 159% at the doses of 5 mg/kg, 10 mg/kg, 20 mg/kg respectively. Pyrotinib in SK-OV-3 ovarian xenograft model shows TGI% on day 21 of 2%, 12%, 83% at the doses of 2.5 mg/kg, 5 mg/kg, 10 mg/kg respectively), which further confirms its robust in vivo antitumor efficacy at 10 mg/kg[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
583.08
Formula
C32H31ClN6O3
CAS 号
1269662-73-8
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 10 mg/mL (17.15 mM; ultrasonic and adjust pH to 6 with HCl)
[1]. Li X, et al. Discovery and development of Pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Jan 21. pii: S0928-0987(17)30043-X.
Cell Assay [1]
Cancer cells (A431, SK-BR-3 and NCI-N87) are treated with a series of concentrations of Pyrotinib for 72 hours. Cell proliferation is determined by a sulforhodamine B (SRB) method. The IC50 values are calculated by the data of inhibition rates of serial concentrations of test compounds[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Rats: Test compounds (include Pyrotinib) are administrated in both intravenous (i.v.) and intragastric (i.g.) for mice to obtain their bioavailability. Plasma samples of nude mice is collected at pre-dose and 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h after the IV administration[1].
Mice: In vivo efficacy studies are performed on BALB/Ca-nude mice (6 to 7 weeks, female) from SLAC. Nude mice are hypodermic inoculated BT-474 human breast cancer cell or SK-OV-3 ovarian cancer cell. After tumor grows to 150-250 mm3, mice are randomly divided into groups and dosed with Pyrotinib (2.5, 5, 10, 20 mg/kg) once daily. The volume of tumors and the weight of the mice are measured and recorded for 2-3 times per week[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Li X, et al. Discovery and development of Pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Jan 21. pii: S0928-0987(17)30043-X.
Dalpiciclib (SHR-6390) is a highly selective, orally bioavailable CDK4/6 inhibitor with comparable potencies against CDK4 (IC50=12.4 nM) and CDK6 (IC50=9.9 nM). Dalpiciclib exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated tumor-suppressor retinoblastoma protein (Rb) and inducing G1 cell cycle arrest[1][2].
IC50 & Target[1]
CDK4
12.4 nM (IC50)
CDK6
9.9 nM (IC50)
体外研究 (In Vitro)
Dalpiciclib (SHR-6390) (0-4 μM) inhibits cell proliferation in a dose-dependent manner[2]. Dalpiciclib (24 hours) significantly blocks phosphorylation of Rb at serine 780 in relative sensitive Eca 109 and KYSE-510 cell lines, but not in relative resistant Eca 9706 cell line. Dalpiciclib induces cell cycle arrest at G1 phase in Eca 109 and KYSE-510 cell lines[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[2]
Cell Line:
Eca 109, Eca 9706, and KYSE-510 ESCC cell lines
Concentration:
0-4 μM
Incubation Time:
72 hours
Result:
Inhibited cell proliferation in a dose-dependent manner, with Eca 109 being the relative sensitive one and Eca 9706 being the relative resistant one.
体内研究 (In Vivo)
Dalpiciclib (SHR-6390) (150 mg/kg; oral gavage; weekly for 3 weeks) shows antitumor activity against ESCC xenografts[2]. Dalpiciclib combines with Paclitaxel (PTX) or Cisplatin (CDDP) offered synergistic inhibitory effects in ESCC xenografts[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
NOD/SCID mice (ESCC PDXs models) [2]
Dosage:
150 mg/kg
Administration:
Oral gavage; weekly for 3 weeks
Result:
The growth of tumor was significantly suppressed in SHR6390 treatment group with various suppressions.
分子量
446.54
Formula
C25H30N6O2
CAS 号
1637781-04-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Zhang P, et al. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. Biomark Res. 2021;9(1):24. Published 2021 Apr 12.
[2]. Wang J, et al. CDK4/6 inhibitor-SHR6390 exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated Rb and inducing G1 cell cycle arrest. J Transl Med. 2017;15(1):127. Published 2017 Jun 2.
Famitinib (SHR1020), an orally active multi-targeted kinase inhibitor, inhibits the activity of c-kit, VEGFR-2 and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM and 6.6 nM, respectively[1]. Famitinib exerts powerful antitumor activity in human gastric cancer cells and xenografts. Famitinib triggers apoptosis[2].
IC50 & Target[2]
VEGFR-2
4.2 nM (IC50)
PDGFRβ
6.6 nM (IC50)
c-kit
2.3 nM (IC50)
体外研究 (In Vitro)
Famitinib inhibits the VEGF-induced proliferation, migration and tubule formation of human umbilical vein endothelial cells, and micro-vessel spouting from matrigel-embedded rat aortic rings[1]. Famitinib inhibits cell proliferation by inducing cell cycle arrest at the G2/M phase and causes cell apoptosis in a dose-dependent manner in gastric cancer cell lines. Famitinib (0.6-20.0 µM) inhibits gastric cancer cell growth in a dose-dependent manner[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[3]
Cell Line:
Human gastric cancer cells BGC-823 and MGC-803
Concentration:
0, 0.6, 1.25, 2.5, 5.0, 10.0 and 20.0 µM
Incubation Time:
24, 48 and 72 hours
Result:
Inhibited cell growth in a dose-dependent manner. The IC50 values in BGC-823 and MGC-803 cells were 3.6 and 3.1 µM, respectively.
体内研究 (In Vivo)
Famitinib exhibits broad and potent anti-tumor activity, leading to regression or growth arrest of various established xenografts derived from human tumor cell lines [1]. Famitinib significantly slows tumor growth in vivo via inhibition of angiogenesis in BGC-823 xenograft models. Famitinib (50 and 100 mg/kg;gavage) reduces xenograft growth in vivo via inhibition of angiogenesis[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Both doses exerted a similar inhibitory power, but greater toxicity was observed. Inhibited BGC-823 xenograft growth (tumor volume, 395.2 vs. 2,690.5 mm3), and animal weights were similar between groups (21.6 vs. 18.7 g).
分子量
410.48
Formula
C23H27FN4O2
CAS 号
1044040-56-3
中文名称
法米替尼
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Liguang Lou, et al. Abstract 3604: Preclinical antitumor study of famitinib, an orally available multi-targeted kinase inhibitor of VEGFR/PDGFR/c-Kit in phase I clinical trials.
[2]. Sai Ge, et al. Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts. Oncol Lett. 2016 Sep;12(3):1763-1768.
SHR168442 is a modulator of retinoid-related orphan receptor gamma (RORγ) with an IC50 value of 0.035 μM.
IC50 & Target
ROR-γ
分子量
532.43
Formula
C23H25Cl2F2N3O3S
CAS 号
2382961-86-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Yan Y, et al. Benzimidazole derivatives as modulators of retinoid-related orphan receptor gamma (rorϒ) and pharmaceutical uses thereof. WO2019213470 A1.
Camrelizumab (SHR-1210) is a potent humanied high-affinity IgG4-κ monoclonal antibody (mAb) to PD-1. Camrelizumab binds PD-1 at a high affinity of 3 nM and inhibits the binding interaction of PD-1 and PD-L1 with an IC50 of 0.70 nM. Camrelizumab acts as anti-PD-1/PD-L1 agent and can be used for cancer research, including NSCLC, ESCC, Hodgkin lymphoma, and advanced HCC et,al[1][2].
IC50 & Target
IC50: 0.70 nM ( PD-1/PD-L1 interaction)[1]
体外研究 (In Vitro)
In a T cell proliferation assay using tuberculin treated peripheral blood mononuclear cells, Camrelizumab induces a T cell proliferation at an EC50 of 0.11 nM. In a similar assay measuring IFN-gamma secretion, Camrelizumab induces IFN-gamma production at an EC50 of 0.38 nM[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Camrelizumab (3 mg/kg) combines with apatinib (200 and 100 mg/kg) inhibits the tumor inhibition rates reached 63.1% and 87.3%, respectively in human PD-1 transgenic mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
CAS 号
1798286-48-2
中文名称
卡瑞利珠单抗
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Kuimin Mei, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer. 2021 Mar;9(3):e002191.
[2]. Jason D Lickliter, et al.A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia. Drug Des Devel Ther
[3]. Caicun Zho, et al.Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med. 2021 Mar;9(3):305-314.
SHR0302 is a potent and orally active all members of the JAK family inhibitor, particularly JAK1. The selectivity of SHR0302 for JAK1 is >10-fold for JAK2, 77-fold for JAK3, 420-fold for Tyk2. SHR0302 inhibits JAK1-STAT3 phosphorylation and induces the apoptosis of hepatic stellate cells. SHR0302 has anti-proliferative and anti-inflammatory effects[1][2].
IC50 & Target[1]
JAK1
JAK2
JAK3
Tyk2
体外研究 (In Vitro)
SHR0302 (1 nM-10 µM; 48 hours; HSCs) treatment displays an inhibitory effect on the proliferation of HSCs in a concentration-dependent manner[2]. SHR0302 (1 nM-10 µM) exerts an inhibitory effect on the activation, proliferation and migration of HSCs[2]. SHR0302 (1 nM-10 µM; 48 hours; HSCs) treatment induces the apoptosis of HSCs[2]. SHR0302 (1 nM-10 µM; 48 hours; HSCs) treatment significantly increases the activation of caspase-3 and Bax in HSCs, and decreases the expression of Bcl-2. SHR0302 also inhibits the activation of Akt signaling pathway[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[2]
Cell Line:
Hepatic stellate cells (HSCs)
Concentration:
1 nM, 10 nM, 100 nM, 1µM, 10 µM
Incubation Time:
48 hours
Result:
Displayed an inhibitory effect on the proliferation of HSCs, and that inhibition ocurred in a concentration-dependent manner.
Apoptosis Analysis[2]
Cell Line:
Hepatic stellate cells (HSCs)
Concentration:
1 nM, 10 nM, 100 nM, 1µM, 10 µM
Incubation Time:
48 hours
Result:
Induced the apoptosis of HSCs.
Western Blot Analysis[2]
Cell Line:
Hepatic stellate cells (HSCs)
Concentration:
1 nM, 10 nM, 100 nM, 1µM, 10 µM
Incubation Time:
48 hours
Result:
Significantly increased the activation of caspase-3 and Bax in HSCs, and decreased the expression of Bcl-2. Also inhibited the activation of Akt signaling pathway.
体内研究 (In Vivo)
SHR0302 (0.3-3.0 mg/kg; intragastric administration; twice a day; for 14 days; male Sprague-Dawley (SD) rats) treatment suppresses the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats[1]. SHR0302 can inhibit the proliferation of T, B and fibroblast-like synoviocytes (FLS), and down-regulates cytokines TNF-α, IL-1β, IL-17 and antibody IgG1, IgG2a levels, and suppresses the proportion of Th17 and total B, and inhibits JAK1-STAT3 phosphorylation[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Sprague-Dawley (SD) rats (150-180 g) injected with complete Freund’s adjuvant (CFA)[1]
Dosage:
0.3 mg/kg,1.0 mg/kg, 3.0 mg/kg
Administration:
Intragastric administration; twice a day; for 14 days
Result:
Suppressed the severity of adjuvant-induced arthritis (AA) rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats.
Clinical Trial
分子量
414.48
Formula
C18H22N8O2S
CAS 号
1445987-21-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Huaxun Wu, et al. JAK1-STAT3 Blockade by JAK Inhibitor SHR0302 Attenuates Inflammatory Responses of Adjuvant-Induced Arthritis Rats and Decreases Th17 and Total B Cells. Joint Bone Spine. 2016 Oct;83(5):525-32.
[2]. Yuan-Jing Gu, et al. Targeted Blockade of JAK/STAT3 Signaling Inhibits Proliferation, Migration and Collagen Production as Well as Inducing the Apoptosis of Hepatic Stellate Cells. Int J Mol Med. 2016 Sep;38(3):903-11.
Dalpiciclib (SHR-6390) hydrochloride is an orally active and highly selective inhibitor of CDK4 and 6 with IC50 values of 12.4 nM and 9.9 nM, respectively[1][2]. Dalpiciclib hydrochloride shows antitumor activity against breast cancer and esophageal squamous cell carcinoma[1][2][3][4].
IC50 & Target
CDK4
12.4 nM (IC50)
CDK6
9.9 nM (IC50)
体外研究 (In Vitro)
Dalpiciclib hydrochloride (0-4 μM, 72 h) inhibits cell proliferation in a dose-dependent manner[3]. Dalpiciclib hydrochloride (0-10 μM, 6 d) inhibits the proliferation of retinoblastoma-positive tumor cell lines[4].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[3]
Cell Line:
Eca 109, Eca 9706 and KYSE-510 ESCC cell lines
Concentration:
0-4 μM
Incubation Time:
72 hours
Result:
Inhibited cell proliferation in a dose-dependent manner, with Eca 109 being the relative sensitive one and Eca 9706 being the relative resistant one.
Cell Viability Assay[4]
Cell Line:
MCF7, MCF7/TR, BT-474/T cell lines
Concentration:
0-10 μM
Incubation Time:
6 days
Result:
Inhibited MCF7/TR cells, parental MCF7 cells and BT-474/T resistant cells with the IC50 values of 229.5, 115.4 and 210.7 nM, respectively.
体内研究 (In Vivo)
Dalpiciclib hydrochloride (oral gavage; 150 mg/kg; once weekly; 3 weeks) shows antitumor activity against ESCC xenografts[3]. Dalpiciclib hydrochloride combined with Paclitaxel (PTX) or Cisplatin (CDDP) offer synergistic inhibitory effects in ESCC xenografts[3]. Dalpiciclib hydrochloride (oral gavage; 37.5 mg/kg, 75 mg/kg, 150 mg/kg; once daily; 30 days) shows antitumor activity in human xenograft models [4].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Oral gavage; 37.5 mg/kg, 75 mg/kg, 150 mg/kg; once daily; 30 days
Result:
Caused regression of all tumor xenografts at the highest dose tested.
分子量
483.01
Formula
C25H31ClN6O2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
溶解性数据
In Vitro:
DMSO : 5 mg/mL (10.35 mM; ultrasonic and warming and heat to 60°C)
配制储备液
浓度溶剂体积质量
1 mg
5 mg
10 mg
1 mM
2.0704 mL
10.3518 mL
20.7035 mL
5 mM
0.4141 mL
2.0704 mL
4.1407 mL
10 mM
0.2070 mL
1.0352 mL
2.0704 mL
参考文献
[1]. Jose Manuel Perez-Garcia, et al. Perez-Garcia JM, Cortes J, Llombart-Cussac A. CDK4/6 inhibitors in breast cancer: spotting the difference. Nat Med. 2021 Nov;27(11):1868-1869.
[2]. Pin Zhang, et al. A phase 1 study of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor in Chinese patients with advanced breast cancer. Biomark Res. 2021 Apr 12;9(1):24.
[3]. Jiayuan Wang, et al. CDK4/6 inhibitor-SHR6390 exerts potent antitumor activity in esophageal squamous cell carcinoma by inhibiting phosphorylated Rb and inducing G1 cell cycle arrest. J Transl Med. 2017 Jun 2;15(1):127.
[4]. Fei Long, et al. Preclinical characterization of SHR6390, a novel CDK 4/6 inhibitor, in vitro and in human tumor xenograft models. Cancer Sci. 2019 Apr;110(4):1420-1430.
