WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200444
CAS#: 852808-04-9
Description: ABT-737 is an orally available inhibitor of the nuclear enzymes poly(ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, ABT-767 selectively binds to PARP 1 and 2, thereby preventing repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances the accumulation of DNA strand breaks and promotes genomic instability eventually leading to apoptosis. ABT-767 may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance.
MedKoo Cat#: 200444
Name: ABT-737
CAS#: 852808-04-9
Chemical Formula: C42H45ClN6O5S2
Exact Mass: 812.25814
Molecular Weight: 813.43
Elemental Analysis: C, 62.02; H, 5.58; Cl, 4.36; N, 10.33; O, 9.83; S, 7.88
Synonym: ABT 737; ABT-737; ABT737.
IUPAC/Chemical Name: (R)-4-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)-3-nitrophenyl)sulfonyl)benzamide
InChi Key: HPLNQCPCUACXLM-PGUFJCEWSA-N
InChi Code: InChI=1S/C42H45ClN6O5S2/c1-46(2)23-22-35(30-55-37-9-4-3-5-10-37)44-40-21-20-38(28-41(40)49(51)52)56(53,54)45-42(50)32-14-18-36(19-15-32)48-26-24-47(25-27-48)29-33-8-6-7-11-39(33)31-12-16-34(43)17-13-31/h3-21,28,35,44H,22-27,29-30H2,1-2H3,(H,45,50)/t35-/m1/s1
SMILES Code: O=C(NS(=O)(C1=CC=C(N[C@H](CCN(C)C)CSC2=CC=CC=C2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=CC=CC=C5C6=CC=C(Cl)C=C6)CC4)C=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | ABT-737 is a selective and BH3 mimetic Bcl-2, Bcl-xL and Bcl-w inhibitor with EC50s of 30.3 nM, 78.7 nM, and 197.8 nM, respectively. |
| In vitro activity: | Both gastric carcinoma cell lines produced Bcl-2, Bcl-XL and Mcl-1 protein, as shown by Western blot analysis (Fig. 1A). Untreated SGC-7901 cells produced a significantly higher level of Bcl-2 protein than MGC-803 cells (P < 0.001), whereas untreated MGC803 cells had a significantly higher level of Mcl-1 protein than SGC-7901 cells (P < 0.001). There was no significant difference in the level of Bcl-XL between the two cell lines. Treatment with ABT-737 resulted in significant inhibition of the proliferation of both SGC-7901 (Fig. 1B) and MGC-803 (Fig. 1C) cells in concentration- and timedependent manners (P < 0.001 for both at 20 µM ABT-737 after 72 h). SGC-7901 cells were more sensitive to ABT-737 than MGC-803 cells. Treatment with ABT-737 (5 µM) resulted in a significant increase in the rate of apoptosis of both SGC-7901 (Fig. 3A) and MGC-803 (Fig. 3B) cells compared with vehicle (P < 0.05). Reference: J Int Med Res. 2012;40(4):1251-64. https://journals.sagepub.com/doi/10.1177/147323001204000404?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed |
| In vivo activity: | Solid SGC-7901 gastric carcinoma xenograft tumours in the control group grew very quickly, reaching a mean ± SD volume of 1007.4 ± 112.3 mm3 at 15 days (Fig. 5A). In contrast, tumours treated with ABT-737 were significantly smaller than control tumours, reaching a mean ± SD volume of 648.6 ± 89.1 and 483.5 ± 71.5 mm3, respectively (P < 0.05 versus control). The rate of apoptosis in vivo was assessed in solid SGC-7901 gastric carcinoma xenograft tumours harvested 15 days after treatment. Consistent with the in vitro data, compared with control tumours, those treated with ABT-737 had a significantly increased rate of apoptosis (210% higher than control; P < 0.05 or P < 0.001, respectively) (Fig. 5B). Reference: J Int Med Res. 2012;40(4):1251-64. https://journals.sagepub.com/doi/10.1177/147323001204000404?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 50.0 | 61.47 |
The following data is based on the product molecular weight 813.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | 1. Sun XP, Zhang X, He C, Qiao H, Jiang X, Jiang H, Sun X. ABT-737 synergizes with arsenic trioxide to induce apoptosis of gastric carcinoma cells in vitro and in vivo. J Int Med Res. 2012;40(4):1251-64. doi: 10.1177/147323001204000404. PMID: 22971477. 2. Clerc P, Carey GB, Mehrabian Z, Wei M, Hwang H, Girnun GD, Chen H, Martin SS, Polster BM. Rapid detection of an ABT-737-sensitive primed for death state in cells using microplate-based respirometry. PLoS One. 2012;7(8):e42487. doi: 10.1371/journal.pone.0042487. Epub 2012 Aug 3. PMID: 22880001; PMCID: PMC3411749. |
| In vivo protocol: | 1. Sun XP, Zhang X, He C, Qiao H, Jiang X, Jiang H, Sun X. ABT-737 synergizes with arsenic trioxide to induce apoptosis of gastric carcinoma cells in vitro and in vivo. J Int Med Res. 2012;40(4):1251-64. doi: 10.1177/147323001204000404. PMID: 22971477. 2. Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, Deng X, Zhai D, Shi YX, Sneed T, Verhaegen M, Soengas M, Ruvolo VR, McQueen T, Schober WD, Watt JC, Jiffar T, Ling X, Marini FC, Harris D, Dietrich M, Estrov Z, McCubrey J, May WS, Reed JC, Andreeff M. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006 Nov;10(5):375-88. doi: 10.1016/j.ccr.2006.10.006. PMID: 17097560. |
1: Huang W, Liu H, Tan W, Wang J. ABT-737 suppresses aberrant Hedgehog pathway and overcomes resistance to smoothened antagonists by blocking Gli. Med Oncol. 2022 Sep 7;39(12):188. doi: 10.1007/s12032-022-01794-w. PMID: 36071246.
2: Lee JM, Kim HS, Kim A, Chang YS, Lee JG, Cho J, Kim EY. ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model. Yonsei Med J. 2022 Jan;63(1):16-25. doi: 10.3349/ymj.2022.63.1.16. PMID: 34913280; PMCID: PMC8688371.
3: Vaux DL. ABT-737, proving to be a great tool even before it is proven in the clinic. Cell Death Differ. 2008 May;15(5):807-8. doi: 10.1038/cdd.2008.31. PMID: 18408737.
4: Yu T, Chen C, Sun Y, Sun H, Li TH, Meng J, Shi X. ABT-737 sensitizes curcumin-induced anti-melanoma cell activity through facilitating mPTP death pathway. Biochem Biophys Res Commun. 2015 Aug 14;464(1):286-91. doi: 10.1016/j.bbrc.2015.06.144. Epub 2015 Jun 24. PMID: 26116776.
5: Yin P, Jia J, Li J, Song Y, Zhang Y, Chen F. ABT-737, a Bcl-2 Selective Inhibitor, and Chloroquine Synergistically Kill Renal Cancer Cells. Oncol Res. 2016;24(1):65-72. doi: 10.3727/096504016X14587366983838. PMID: 27178823; PMCID: PMC7838628.
6: Cheng R, Liu X, Wang Z, Tang K. ABT‑737, a Bcl‑2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis. Mol Med Rep. 2021 Jun;23(6):412. doi: 10.3892/mmr.2021.12051. Epub 2021 Mar 31. PMID: 33786632; PMCID: PMC8025475.
7: Reuland SN, Goldstein NB, Partyka KA, Smith S, Luo Y, Fujita M, Gonzalez R, Lewis K, Norris DA, Shellman YG. ABT-737 synergizes with Bortezomib to kill melanoma cells. Biol Open. 2012 Feb 15;1(2):92-100. doi: 10.1242/bio.2011035. Epub 2011 Nov 16. PMID: 23213401; PMCID: PMC3507205.
8: Ou YC, Li JR, Wang JD, Chen WY, Kuan YH, Yang CP, Liao SL, Lu HC, Chen CJ. Aspirin restores ABT-737-mediated apoptosis in human renal carcinoma cells. Biochem Biophys Res Commun. 2018 Jul 12;502(2):187-193. doi: 10.1016/j.bbrc.2018.05.142. Epub 2018 May 24. PMID: 29792865.
9: Zhang F, Yu X, Liu X, Zhou T, Nie T, Cheng M, Liu H, Dai M, Zhang B. ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway. Oncol Rep. 2017 Oct;38(4):2301-2308. doi: 10.3892/or.2017.5909. Epub 2017 Aug 14. PMID: 28849162.
10: Cristofanon S, Fulda S. ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells. Cell Death Dis. 2012 Nov 29;3(11):e432. doi: 10.1038/cddis.2012.163. PMID: 23190604; PMCID: PMC3542599.
11: Yuan J, Song J, Chen C, Lv X, Bai J, Yang J, Zhou Y. Combination of ruxolitinib with ABT-737 exhibits synergistic effects in cells carrying concurrent JAK2V617F and ASXL1 mutations. Invest New Drugs. 2022 Dec;40(6):1194-1205. doi: 10.1007/s10637-022-01297-5. Epub 2022 Aug 31. PMID: 36044173.
12: Kim EY, Jung JY, Kim A, Chang YS, Kim SK. ABT-737 Synergizes with Cisplatin Bypassing Aberration of Apoptotic Pathway in Non-small Cell Lung Cancer. Neoplasia. 2017 Apr;19(4):354-363. doi: 10.1016/j.neo.2017.02.008. Epub 2017 Mar 17. PMID: 28319809; PMCID: PMC5358954.
13: Kim LH, Shin JA, Jang B, Yang IH, Won DH, Jeong JH, Chung TH, Cho NP, Cho SD. Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells. Arch Oral Biol. 2017 Jan;73:1-6. doi: 10.1016/j.archoralbio.2016.08.034. Epub 2016 Aug 31. PMID: 27632413.
14: Avsar Abdik E, Kaleagasioglu F, Abdik H, Sahin F, Berger MR. ABT-737 and erufosine combination against castration-resistant prostate cancer: a promising but cell-type specific response associated with the modulation of anti-apoptotic signaling. Anticancer Drugs. 2019 Apr;30(4):383-393. doi: 10.1097/CAD.0000000000000736. PMID: 30557204.
15: Wei H, Harper MT. ABT-737 Triggers Caspase-Dependent Inhibition of Platelet Procoagulant Extracellular Vesicle Release during Apoptosis and Secondary Necrosis In Vitro. Thromb Haemost. 2019 Oct;119(10):1665-1674. doi: 10.1055/s-0039-1693694. Epub 2019 Sep 7. Erratum in: Thromb Haemost. 2019 Oct;119(10):e1. PMID: 31493778; PMCID: PMC6768798.
16: Fitzgerald DJ, Moskatel E, Ben-Josef G, Traini R, Tendler T, Sharma A, Antignani A, Mussai F, Wayne A, Kreitman RJ, Pastan I. Enhancing immunotoxin cell-killing activity via combination therapy with ABT-737. Leuk Lymphoma. 2011 Jun;52 Suppl 2(Suppl 2):79-81. doi: 10.3109/10428194.2011.569961. PMID: 21599608; PMCID: PMC7450489.
17: Bodet L, Gomez-Bougie P, Touzeau C, Dousset C, Descamps G, Maïga S, Avet- Loiseau H, Bataille R, Moreau P, Le Gouill S, Pellat-Deceunynck C, Amiot M. ABT-737 is highly effective against molecular subgroups of multiple myeloma. Blood. 2011 Oct 6;118(14):3901-10. doi: 10.1182/blood-2010-11-317438. Epub 2011 Aug 11. PMID: 21835956.
18: Lever JR, Fergason-Cantrell EA. Allosteric modulation of sigma receptors by BH3 mimetics ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax). Pharmacol Res. 2019 Apr;142:87-100. doi: 10.1016/j.phrs.2019.01.040. Epub 2019 Feb 3. PMID: 30721730.
19: Parrondo R, de Las Pozas A, Reiner T, Perez-Stable C. ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells. PeerJ. 2013 Sep 12;1:e144. doi: 10.7717/peerj.144. PMID: 24058878; PMCID: PMC3775631.
20: Woo SM, Min KJ, Seo BR, Seo YH, Jeong YJ, Kwon TK. YM155 enhances ABT-737-mediated apoptosis through Mcl-1 downregulation in Mcl-1-overexpressed cancer cells. Mol Cell Biochem. 2017 May;429(1-2):91-102. doi: 10.1007/s11010-016-2938-0. Epub 2017 Jan 24. PMID: 28120212.
