WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H407213
CAS#: 1235034-55-5
Description: A-1155463 is a highly potent and selective BCL-XL inhibitor. A-1155463 is substantially more potent against BCL-XL-dependent cell lines relative to WEHI-539, while possessing none of its inherent pharmaceutical liabilities. A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. A-1155463 thus represents an excellent tool molecule for studying BCL-XL biology as well as a productive lead structure for further optimization.
Hodoodo Cat#: H407213
Name: A-1155463
CAS#: 1235034-55-5
Chemical Formula: C35H32FN5O4S2
Exact Mass: 669.19
Molecular Weight: 669.790
Elemental Analysis: C, 62.76; H, 4.82; F, 2.84; N, 10.46; O, 9.55; S, 9.57
Synonym: A-1155463; A 1155463; A1155463.
IUPAC/Chemical Name: 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-(4-(3-(dimethylamino)prop-1-yn-1-yl)-2-fluorophenoxy)propyl)thiazole-4-carboxylic acid
InChi Key: SOYCFODXNRVBTI-UHFFFAOYSA-N
InChi Code: InChI=1S/C35H32FN5O4S2/c1-40(2)17-6-8-22-14-15-28(26(36)20-22)45-19-7-13-30-31(33(43)44)38-35(47-30)41-18-16-23-9-5-10-24(25(23)21-41)32(42)39-34-37-27-11-3-4-12-29(27)46-34/h3-5,9-12,14-15,20H,7,13,16-19,21H2,1-2H3,(H,43,44)(H,37,39,42)
SMILES Code: O=C(C1=C(CCCOC2=CC=C(C#CCN(C)C)C=C2F)SC(N3CC4=C(C=CC=C4C(NC5=NC6=CC=CC=C6S5)=O)CC3)=N1)O
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
More Info:
Biological target: | |
In vitro activity: | |
In vivo activity: |
The following data is based on the product molecular weight 669.79 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 |
Formulation protocol: | |
In vitro protocol: | |
In vivo protocol: |
1: Tao ZF, Hasvold L, Wang L, Wang X, Petros AM, Park CH, Boghaert ER, Catron ND, Chen J, Colman PM, Czabotar PE, Deshayes K, Fairbrother WJ, Flygare JA, Hymowitz SG, Jin S, Judge RA, Koehler MF, Kovar PJ, Lessene G, Mitten MJ, Ndubaku CO, Nimmer P, Purkey HE, Oleksijew A, Phillips DC, Sleebs BE, Smith BJ, Smith ML, Tahir SK, Watson KG, Xiao Y, Xue J, Zhang H, Zobel K, Rosenberg SH, Tse C, Leverson JD, Elmore SW, Souers AJ. Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity. ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93. doi: 10.1021/ml5001867. PMID: 25313317; PMCID: PMC4190639.
2: Wang L, Doherty GA, Judd AS, Tao ZF, Hansen TM, Frey RR, Song X, Bruncko M, Kunzer AR, Wang X, Wendt MD, Flygare JA, Catron ND, Judge RA, Park CH, Shekhar S, Phillips DC, Nimmer P, Smith ML, Tahir SK, Xiao Y, Xue J, Zhang H, Le PN, Mitten MJ, Boghaert ER, Gao W, Kovar P, Choo EF, Diaz D, Fairbrother WJ, Elmore SW, Sampath D, Leverson JD, Souers AJ. Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-XL Inhibitor. ACS Med Chem Lett. 2020 Mar 30;11(10):1829-1836. doi: 10.1021/acsmedchemlett.9b00568. PMID: 33062160; PMCID: PMC7549103.
3: Ramesh P, Di Franco S, Atencia Taboada L, Zhang L, Nicotra A, Stassi G, Medema JP. BCL-XL inhibition induces an FGFR4-mediated rescue response in colorectal cancer. Cell Rep. 2022 Feb 15;38(7):110374. doi: 10.1016/j.celrep.2022.110374. PMID: 35172148.
4: Wakui N, Yoshino R, Yasuo N, Ohue M, Sekijima M. Exploring the selectivity of inhibitor complexes with Bcl-2 and Bcl-XL: A molecular dynamics simulation approach. J Mol Graph Model. 2018 Jan;79:166-174. doi: 10.1016/j.jmgm.2017.11.011. Epub 2017 Nov 23. PMID: 29197725.
5: Zhang H, Xue J, Hessler P, Tahir SK, Chen J, Jin S, Souers AJ, Leverson JD, Lam LT. Genomic analysis and selective small molecule inhibition identifies BCL-X(L) as a critical survival factor in a subset of colorectal cancer. Mol Cancer. 2015 Jul 2;14:126. doi: 10.1186/s12943-015-0397-y. PMID: 26134786; PMCID: PMC4487849.
6: Tao ZF, Wang X, Chen J, Ingram JP, Jin S, Judge RA, Kovar PJ, Park C, Sun C, Wakefield BD, Zhou L, Zhang H, Elmore SW, Phillips DC, Judd AS, Leverson JD, Souers AJ. Structure-Based Design of A-1293102, a Potent and Selective BCL-XL Inhibitor. ACS Med Chem Lett. 2021 May 12;12(6):1011-1016. doi: 10.1021/acsmedchemlett.1c00162. PMID: 34141086; PMCID: PMC8201748.
7: Xu D, Liang SQ, Yang Z, Yang H, Bruggmann R, Oberhaensli S, Berezowska S, Marti TM, Hall SRR, Dorn P, Kocher GJ, Schmid RA, Peng RW. Malignant pleural mesothelioma co-opts BCL-XL and autophagy to escape apoptosis. Cell Death Dis. 2021 Apr 15;12(4):406. doi: 10.1038/s41419-021-03668-x. PMID: 33859162; PMCID: PMC8050302.
8: Tsuji K, Kida Y, Koshikawa N, Yamamoto S, Shinozaki Y, Watanabe T, Lin J, Nagase H, Takenaga K. Suppression of non-small-cell lung cancer A549 tumor growth by an mtDNA mutation-targeting pyrrole-imidazole polyamide- triphenylphosphonium and a senolytic drug. Cancer Sci. 2022 Apr;113(4):1321-1337. doi: 10.1111/cas.15290. Epub 2022 Feb 16. PMID: 35112436; PMCID: PMC8990788.
9: Sun WC, Pei L. rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes. J Neurochem. 2016 Jul;138(2):233-42. doi: 10.1111/jnc.13647. Epub 2016 Jun 6. PMID: 27121046.
10: Phillips DC, Xiao Y, Lam LT, Litvinovich E, Roberts-Rapp L, Souers AJ, Leverson JD. Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199). Blood Cancer J. 2015 Nov 13;5(11):e368. doi: 10.1038/bcj.2015.88. Erratum in: Blood Cancer J. 2016;6:e403. PMID: 26565405; PMCID: PMC4670945.
11: Sun WC, Pei L. Dexmedetomidine attenuates propofol-induced apoptosis of neonatal hippocampal astrocytes by inhibiting the Bcl2l1 signalling pathway. Eur J Neurosci. 2021 Dec;54(11):7775-7789. doi: 10.1111/ejn.15517. Epub 2021 Nov 23. PMID: 34734676.
12: Ren Y, Huang SH, Macedo AB, Ward AR, Alberto WDC, Klevorn T, Leyre L, Copertino DC, Mota TM, Chan D, Truong R, Rohwetter T, Zumbo P, Dündar F, Betel D, Kovacs C, Benko E, Bosque A, Jones RB. Selective BCL-XL Antagonists Eliminate Infected Cells from a Primary-Cell Model of HIV Latency but Not from Ex Vivo Reservoirs. J Virol. 2021 Jul 12;95(15):e0242520. doi: 10.1128/JVI.02425-20. Epub 2021 Jul 12. PMID: 33980597; PMCID: PMC8274617.
13: Li L, Li P, Song H, Ma X, Zeng S, Peng Y, Zhang G. Targeting entry into mitochondria for increased anticancer efficacy of BCL-XL-selective inhibitors in lung cancer. Pharmacol Res. 2022 Mar;177:106095. doi: 10.1016/j.phrs.2022.106095. Epub 2022 Jan 21. PMID: 35074525.
14: Ianevski A, Kulesskiy E, Krpina K, Lou G, Aman Y, Bugai A, Aasumets K, Akimov Y, Bulanova D, Gildemann K, Arutyunyan AF, Susova OY, Zhuze AL, Ji P, Wang W, Holien T, Bugge M, Zusinaite E, Oksenych V, Lysvand H, Gerhold JM, Bjørås M, Johansen P, Waage A, Heckman CA, Fang EF, Kainov DE. Chemical, Physical and Biological Triggers of Evolutionary Conserved Bcl-xL-Mediated Apoptosis. Cancers (Basel). 2020 Jun 25;12(6):1694. doi: 10.3390/cancers12061694. PMID: 32630560; PMCID: PMC7352625.
15: Slomp A, Moesbergen LM, Gong JN, Cuenca M, von dem Borne PA, Sonneveld P, Huang DCS, Minnema MC, Peperzak V. Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting. Blood Adv. 2019 Dec 23;3(24):4202-4214. doi: 10.1182/bloodadvances.2019000702. PMID: 31856269; PMCID: PMC6929383.
16: Kerkhofs M, Vervloessem T, Stopa KB, Smith VM, Vogler M, Bultynck G. DLBCL Cells with Acquired Resistance to Venetoclax Are Not Sensitized to BIRD-2 But Can Be Resensitized to Venetoclax through Bcl-XL Inhibition. Biomolecules. 2020 Jul 21;10(7):1081. doi: 10.3390/biom10071081. PMID: 32708132; PMCID: PMC7408247.
17: Wang Q, Wan J, Zhang W, Hao S. MCL-1 or BCL-xL-dependent resistance to the BCL-2 antagonist (ABT-199) can be overcome by specific inhibitor as single agents and in combination with ABT-199 in acute myeloid leukemia cells. Leuk Lymphoma. 2019 Sep;60(9):2170-2180. doi: 10.1080/10428194.2018.1563694. Epub 2019 Jan 10. PMID: 30626241.
18: Yu X, Dobrikov M, Keir ST, Gromeier M, Pastan IH, Reisfeld R, Bigner DD, Chandramohan V. Synergistic antitumor effects of 9.2.27-PE38KDEL and ABT-737 in primary and metastatic brain tumors. PLoS One. 2019 Jan 9;14(1):e0210608. doi: 10.1371/journal.pone.0210608. PMID: 30625226; PMCID: PMC6326518.
19: Rose JC, Stephany JJ, Wei CT, Fowler DM, Maly DJ. Rheostatic Control of Cas9-Mediated DNA Double Strand Break (DSB) Generation and Genome Editing. ACS Chem Biol. 2018 Feb 16;13(2):438-442. doi: 10.1021/acschembio.7b00652. Epub 2017 Sep 15. PMID: 28895730; PMCID: PMC5821106.
20: Bulanova D, Ianevski A, Bugai A, Akimov Y, Kuivanen S, Paavilainen H, Kakkola L, Nandania J, Turunen L, Ohman T, Ala-Hongisto H, Pesonen HM, Kuisma MS, Honkimaa A, Walton EL, Oksenych V, Lorey MB, Guschin D, Shim J, Kim J, Than TT, Chang SY, Hukkanen V, Kulesskiy E, Marjomaki VS, Julkunen I, Nyman TA, Matikainen S, Saarela JS, Sane F, Hober D, Gabriel G, De Brabander JK, Martikainen M, Windisch MP, Min JY, Bruzzone R, Aittokallio T, Vähä-Koskela M, Vapalahti O, Pulk A, Velagapudi V, Kainov DE. Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins. Viruses. 2017 Sep 25;9(10):271. doi: 10.3390/v9100271. PMID: 28946654; PMCID: PMC5691623.