BM-PEG3 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
IC50 & Target
PEGs
体外研究 (In Vitro)
PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
352.34
Formula
C16H20N2O7
CAS 号
86099-06-1
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]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562.
BM-PEG3 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
IC50 & Target
PEGs
体外研究 (In Vitro)
PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins[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.
分子量
352.34
Formula
C16H20N2O7
CAS 号
86099-06-1
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]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562.
BM-PEG3 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
IC50 & Target
PEGs
体外研究 (In Vitro)
PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
352.34
Formula
C16H20N2O7
CAS 号
86099-06-1
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]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562.
BM 957 is a potent Bcl-2 and Bcl-xL inhibitor, with Kis of 1.2, <1 nm and IC50s of 5.4, 6.0 nM respectively.
IC50 & Target[1]
Bcl-2
5.4 nM (IC50)
Bcl-xL
6.0 nM (IC50)
Bcl-2
1.2 nM (Ki)
Bcl-xL
<1 nM (Ki)
体外研究 (In Vitro)
BM 957 (Compound 30) with ethyl and compound 31 with isopropyl bind to both Bcl-2 and Bcl-xL with very high affinities. While BM 957 and 31 bind to Bcl-2 with IC50 values of 5.4 and 4.0 nM, respectively (Ki values=1.2 and 0.8 nM, respectively), they bind to Bcl-xL with IC50 values of 6.0 and 3.9 nM, respectively (Ki values < 1 nM). BM 957 has IC50 values of 21 nM and 22 nM, respectively, in these two cancer cell lines (H1417 and H146 cell lines). All these compounds induce cell death in a dose-dependent manner but have different potencies. While BM 957 and 31 are several times more potent than 1 and 2. BM 957 at 10 nM, 28 at 100 nM and 2 at 30 nM all induce clear cleavage of PARP and activation of caspase-3 and have similar effects. Hence, the potencies for these three compounds in induction of cleavage of PARP and activation of caspase-3 in the H146 cells are consistent with their potencies in induction of cell death[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)
It is found that 28 at 50 mg/kg, BM 957 at 25 mg/kg and 31 at 10 mg/kg, daily, intravenous dosing, 5 days a week for 2 weeks are well tolerated in SCID mice and the animals have less than 10% of weight loss. Higher doses of these compounds (75 mg/kg for 28, 50 mg/kg for 30 and 25 mg/kg for 31) cause more than 10% of weight loss. Mice bearing H146 tumors are given a single i.v. dose of 28 at 50 mg/kg or BM 957 at 25 mg/kg. It showed that although compound 28 at 50 mg/kg effectively inhibits tumor growth, it fails to induce tumor regression. In contrast, BM 957 at 25 mg/kg is capable of achieving complete tumor regression. Of 7 mice treated with BM 957, all mice are tumor-free at day 47 and five (71%) remained tumor-free on day 58. Similar to the data obtained from our MTD experiment, both compounds 28 and BM 957 are well tolerated in tumor-bearing animals. All treated animals experienced less than 10% weight loss compared to the vehicle control and all regained their weight quickly after the treatments are finished. This in vivo experiment thus establish that BM 957 achieves complete and durable tumor regression in the H146 xenograft tumor model and is more efficacious than 28[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.
分子量
1065.68
Formula
C52H56ClF3N6O7S3
CAS 号
1391107-54-2
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]. Chen J, et al. Structure-based discovery of BM-957 as a potent small-molecule inhibitor of Bcl-2 and Bcl-xL capable of achieving complete tumor regression. J Med Chem. 2012 Oct 11;55(19):8502-14.
Cell Assay [1]
Two cancer cell lines (H1417 and H146 cell lines) are used. Induction of cell death by compounds (e.g., BM 957) in the H146 cell line. Cells are treated with different concentrations of the compounds (e.g., BM 957: 10, 30, 100 nM) for 24 hr. Cell viability is determined using a trypan blue exclusion assay[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]
Mice[1] Induction of cleavage of PARP and caspase-3 in H146 xenograft tumors by compounds 28 and BM 957. SCID mice bearing H146 xenograft tumors (100-200 mm3) are treated with vehicle control, single dose of 28 (50 mg/kg, i.v.) or BM 957 (25 mg/kg, i.v.). SCID mice bearing xenograft tumors (100 mm3) are treated with vehicle control, compound 28 at 50 mg/kg, i.v. or BM 957 at 25 mg/kg, i.v., daily, 5 days a week for two weeks. The tumor growth inhibition for both compounds is statistically highly significant with p=0.0033 for compound 28 versus vehicle control and p=0.0006 for BM 957 versus vehicle control, respectively, when the mean tumor volume reaches 750 mm3 in the vehicle treated group in both experiments[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]. Chen J, et al. Structure-based discovery of BM-957 as a potent small-molecule inhibitor of Bcl-2 and Bcl-xL capable of achieving complete tumor regression. J Med Chem. 2012 Oct 11;55(19):8502-14.
Carvedilol-d5 is deuterium labeled Carvedilol. Carvedilol (BM 14190) is a non-selective β/α-1 blocker[1]. Carvedilol inhibits lipid peroxidation in a dose-dependent manner with an IC50 of 5 μM. Carvedilol is a multiple action antihypertensive agent with potential use in angina and congestive heart failure[2]. Carvedilol is an autophagy inducer that inhibits the NLRP3 inflammasome[3].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
411.51
Formula
C24H21D5N2O4
CAS 号
929106-58-1
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]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Eggertsen R, et al. Acute haemodynamic effects of carvedilol (BM 14190), a new combined beta-adrenoceptor blocker and precapillary vasodilating agent, in hypertensive patients. Eur J Clin Pharmacol. 1984;27(1):19-22.
[3]. Feuerstein GZ, et al. Myocardial protection by the novel vasodilating beta-blocker, carvedilol: potential relevance of anti-oxidant activity. J Hypertens Suppl. 1993 Jun;11(4):S41-8.
[4]. Wong WT, et al. Repositioning of the β-Blocker Carvedilol as a Novel Autophagy Inducer That Inhibits the NLRP3 Inflammasome. Front Immunol. 2018 Aug 22;9:1920.
BM-1197 is a potent and selective inhibitor of dual Bcl-2/Bcl-xL, with IC50s of 3.5 nM and 5.2 nM for Bcl-2 and Bcl-xL, respectively. BM-1197 exhibits antitumor effects both in vitro and in vivo[1][2].
IC50 & Target[1]
Bcl-2
3.5 nM (IC50)
Bcl-xL
5.2 nM (IC50)
体外研究 (In Vitro)
BM-1197 (2-2000 nM; 3 d) has marginal cytotoxicity against wild-type mouse embryonic fibroblast (MEF) cells but exerts potent growth-inhibitory activity in the MCL1−/− cells[1]. BM-1197 shows potent growth-inhibitory activities in 7 small cell lung cancer (SCLC) cell lines with IC50s <100 nm, moderate activity in 3 sclc cell lines with ic50s of ∼600 nM and weak activity in 2 SCLC cell lines with IC50s >2000 nM[1]. BM-1197 (100 nM; 16 h) potently induces apoptosis in H146 cells[1]. BM-1197 (100 nM; 2 h) disrupts the association between Bcl-xl and Puma or Bim in H146 cells[1]. BM-1197 (100 nM; 0.5-2 h) induces Bax translocation, and it (3-30 nM; 2 h) induces cytochrome c release in H146 cells[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
MEF/MCL1−/− cells
Concentration:
2, 20, 200, 2000 nM
Incubation Time:
3 days
Result:
Inhibited MCL1−/− cells proliferation.
Apoptosis Analysis[1]
Cell Line:
H146 cells
Concentration:
100 nM
Incubation Time:
16 hours
Result:
Induced apoptosis in a strictly Bax/Bak-dependent manner.
Western Blot Analysis[1]
Cell Line:
H146 cells
Concentration:
100 nM
Incubation Time:
2 hours
Result:
Attenuated the associations between Bcl-xL and BimEL or Puma.
体内研究 (In Vivo)
BM-1197 (10 mg/kg; i.v. daily 5 days per week for 2 weeks) results in rapid and complete tumor regression in all 8 mice in H146 and H1963 tumor model[1]. BM-1197 (15 mg/kg; i.v.) causes thrombocytopenia in mice but the effect is reversible even at highly efficacious doses[1]. BM-1197 (10 mg/kg; i.v. qd) exerts a strong anti-tumor effect and is well tolerated in OCI-Ly8 xenograft models[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
SCID mice bearing H146 cells[1]
Dosage:
10 mg/kg
Administration:
I.v. daily 5 days per week for 2 weeks
Result:
Remained tumor free for at least 32 days after the end of the treatment.
分子量
1131.78
Formula
C53H59ClF4N6O7S4
CAS 号
1391107-89-3
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]. Bai L, et, al. BM-1197: a novel and specific Bcl-2/Bcl-xL inhibitor inducing complete and long-lasting tumor regression in vivo. PLoS One. 2014 Jun 5; 9(6): e99404.
[2]. Sun YL, et, al. A novel Bcl-2 inhibitor, BM-1197, induces apoptosis in malignant lymphoma cells through the endogenous apoptotic pathway. BMC Cancer. 2019 Dec 31; 20(1):1.
Imexon (BM 06002) is an iminopyrrolidone aziridine with anti-cancer activity.
体外研究 (In Vitro)
Imexon (BM 06002) induces oxidative stress in the ER, activates an ER stress response. Imexon (BM 06002) does not significantly alter the levels of eIF2B5, however there is a dose-dependent increase in the phosphorylation of eIF2alpha, as well as an increase in the levels of GTP exchange protein eIF2B2 in MiaPaCa-2, Panc-1, and BxPC3 cells[1]. Imexon (BM 06002) induces single-stranded breaks in the human A375 melanoma cells but only significantly at the highest concentrations for each agent compared to controls. Imexon plus DTIC cytotoxicity is additive[2]. Imexon (BM 06002) show inhibitory activities against MiaPaCa-2, Panc-1 and BxPC3, with IC50s of 275.5 ± 54.2, 147.4 ± 4.7 and 355.7 ± 114.7 μM[3].
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)
Imexon (BM 06002) in combination with DTIC results in an increase in the peak plasma imexon level in non-tumor-bearing mice. The combination of both drugs increases plasma imexon AUC by 22% (p=0.026). Imexon (BM 06002) (100 mg/kg/day, i.v.) treatment decreases the body weight of SCID mice bearing human A375 melanoma tumors, but there is no significant difference in tumor growth[2]. Imexon (BM 06002) (100 mg/kg) in combination with GEM shows synergistic inhibition of Panc-1 tumor growth in SCID mice.
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
111.10
Formula
C4H5N3O
CAS 号
59643-91-3
中文名称
亚美克松
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Sheveleva EV, et al. Imexon induces an oxidative endoplasmic reticulum stress response in pancreatic cancer cells. Mol Cancer Res. 2012 Mar;10(3):392-400.
[2]. Samulitis BK, et al. Interaction of dacarbazine and imexon, in vitro and in vivo, in human A375 melanoma cells. Anticancer Res. 2011 Sep;31(9):2781-5.
[3]. Roman NO, et al. Imexon enhances gemcitabine cytotoxicity by inhibition of ribonucleotide reductase. Cancer Chemother Pharmacol. 2011 Jan;67(1):183-92.
Cell Assay [1]
Cell survival for the siRNA screening experiments are calculated by the conversion of resazurin to resorufin by metabolically active cells resulting in a fluorescent product. Confirmatory growth inhibition assays with eIF2b silencing are done using the methyl-thiazolyl-diphenyl-tetrazolium bromide (MTT) assay. Cell growth inhibition data are expressed as percent survival, compared to untreated cells. The IC50 is defined as the drug concentration required to produce 50% growth inhibition.
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 [2]
The effect of the combination on tumor growth in vivo is evaluated in 25-30 g male SCID mice (n=8/group). Mice receive 5×106 A375 cells subcutaneously and are pair matched on day 30, when the average tumor burden is approximately 100 mm3. Treatment begins the following day, as follows: (i) saline vehicle control; (ii) 80 mg/kg/day DTIC; (iii) 100 mg/kg/day imexon; (iv) a combination of both drugs at the same doses. Drugs are administered (i.p.) for nine consecutive days and imexon is administered 15 min before DTIC when combined. Measurement of tumor burden and body weights are made every 3-4 days. Tumor burden (mm3) is calculated as (length × width2)/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.
参考文献
[1]. Sheveleva EV, et al. Imexon induces an oxidative endoplasmic reticulum stress response in pancreatic cancer cells. Mol Cancer Res. 2012 Mar;10(3):392-400.
[2]. Samulitis BK, et al. Interaction of dacarbazine and imexon, in vitro and in vivo, in human A375 melanoma cells. Anticancer Res. 2011 Sep;31(9):2781-5.
[3]. Roman NO, et al. Imexon enhances gemcitabine cytotoxicity by inhibition of ribonucleotide reductase. Cancer Chemother Pharmacol. 2011 Jan;67(1):183-92.
Carvedilol (BM 14190) is a non-selective β/α-1 blocker[1]. Carvedilol inhibits lipid peroxidation in a dose-dependent manner with an IC50 of 5 μM. Carvedilol is a multiple action antihypertensive agent with potential use in angina and congestive heart failure[2]. Carvedilol is an autophagy inducer that inhibits the NLRP3 inflammasome[3].
Superoxide generation by activated human neutrophils in vitro is inhibited by Carvedilol with an IC50 of 28 μM. Carvedilol is shown to scavenge oxygen free radicals in a cell-free system with an IC50 of 25 μM[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.
Clinical Trial
分子量
406.47
Formula
C24H26N2O4
CAS 号
72956-09-3
中文名称
卡维地洛；卡维地罗
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Eggertsen R, et al. Acute haemodynamic effects of carvedilol (BM 14190), a new combined beta-adrenoceptor blocker and precapillary vasodilating agent, in hypertensive patients. Eur J Clin Pharmacol. 1984;27(1):19-22.
[2]. Feuerstein GZ, et al. Myocardial protection by the novel vasodilating beta-blocker, carvedilol: potential relevance of anti-oxidant activity. J Hypertens Suppl. 1993 Jun;11(4):S41-8.
[3]. Wong WT, et al. Repositioning of the β-Blocker Carvedilol as a Novel Autophagy Inducer That Inhibits the NLRP3 Inflammasome. Front Immunol. 2018 Aug 22;9:1920.
Carvedilol-d4 (BM 14190-d4) is the deuterium labeled Carvedilol. Carvedilol (BM 14190) is a non-selective β/α-1 blocker[1]. Carvedilol inhibits lipid peroxidation in a dose-dependent manner with an IC50 of 5 μM. Carvedilol is a multiple action antihypertensive agent with potential use in angina and congestive heart failure[2]. Carvedilol is an autophagy inducer that inhibits the NLRP3 inflammasome[3].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
410.50
Formula
C24H22D4N2O4
CAS 号
1133705-56-2
中文名称
卡维地洛 d4
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]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Eggertsen R, et al. Acute haemodynamic effects of carvedilol (BM 14190), a new combined beta-adrenoceptor blocker and precapillary vasodilating agent, in hypertensive patients. Eur J Clin Pharmacol. 1984;27(1):19-22.
[3]. Feuerstein GZ, et al. Myocardial protection by the novel vasodilating beta-blocker, carvedilol: potential relevance of anti-oxidant activity. J Hypertens Suppl. 1993 Jun;11(4):S41-8.
[4]. Wong WT, et al. Repositioning of the β-Blocker Carvedilol as a Novel Autophagy Inducer That Inhibits the NLRP3 Inflammasome. Front Immunol. 2018 Aug 22;9:1920.
