A-1331852 - CAS 1430844-80-6
Catalog number: B0084-007703
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C38H38N6O3S
Molecular Weight:
658.81
COA:
Inquire
Targets:
Bcl-2 Family
Description:
A-1331852, a substituted benzothiazole, is a high affinity BH3 mimetic Ligand of BCL protein BCL-XL (Ki≤ 10 pM). A-1331852 is an orally apoptosis-inducing agent that may have potential as improved cancer therapeutics.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-007703 100 mg $998 In stock
Bulk Inquiry
Brife Description:
A potent and selective inhibitor of BCL-XL
Synonyms:
3-(1-(((3r,5r,7r)-adamantan-1-yl)methyl)-5-methyl-1H-pyrazol-4-yl)-6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)picolinic acid; A-1331852; A 1331852; A1331852; ABT-263; ABT-199
Solubility:
DMSO: ≥ 12 mg/mL
Storage:
Store in a cool and dry place (or refer to the Certificate of Analysis).
MSDS:
Inquire
Density:
1.50±0.1 g/cm3
InChIKey:
QCQQONWEDCOTBV-UHFFFAOYSA-N
InChI:
1S/C38H38N6O3S/c1-22-29(19-39-44(22)21-38-16-23-13-24(17-38)15-25(14-23)18-38)27-9-10-33(41-34(27)36(46)47)43-12-11-26-5-4-6-28(30(26)20-43)35(45)42-37-40-31-7-2-3-8-32(31)48-37/h2-10,19,23-25H,11-18,20-21H2,1H3,(H,46,47)(H,40,42,45)
Canonical SMILES:
CC1=C(C=NN1CC23CC4CC(C2)CC(C4)C3)C5=C(N=C(C=C5)N6CCC7=CC=CC(=C7C6)C(=O)NC8=NC9=CC=CC=C9S8)C(=O)O
1.Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models.
Punnoose EA;Leverson JD;Peale F;Boghaert ER;Belmont LD;Tan N;Young A;Mitten M;Ingalla E;Darbonne WC;Oleksijew A;Tapang P;Yue P;Oeh J;Lee L;Maiga S;Fairbrother WJ;Amiot M;Souers AJ;Sampath D Mol Cancer Ther. 2016 May;15(5):1132-44. doi: 10.1158/1535-7163.MCT-15-0730. Epub 2016 Mar 3.
BCL-2 family proteins dictate survival of human multiple myeloma cells, making them attractive drug targets. Indeed, multiple myeloma cells are sensitive to antagonists that selectively target prosurvival proteins such as BCL-2/BCL-XL (ABT-737 and ABT-263/navitoclax) or BCL-2 only (ABT-199/GDC-0199/venetoclax). Resistance to these three drugs is mediated by expression of MCL-1. However, given the selectivity profile of venetoclax it is unclear whether coexpression of BCL-XL also affects antitumor responses to venetoclax in multiple myeloma. In multiple myeloma cell lines (n = 21), BCL-2 is expressed but sensitivity to venetoclax correlated with high BCL-2 and low BCL-XL or MCL-1 expression. Multiple myeloma cells that coexpress BCL-2 and BCL-XL were resistant to venetoclax but sensitive to a BCL-XL-selective inhibitor (A-1155463). Multiple myeloma xenograft models that coexpressed BCL-XL or MCL-1 with BCL-2 were also resistant to venetoclax. Resistance to venetoclax was mitigated by cotreatment with bortezomib in xenografts that coexpressed BCL-2 and MCL-1 due to upregulation of NOXA, a proapoptotic factor that neutralizes MCL-1. In contrast, xenografts that expressed BCL-XL, MCL-1, and BCL-2 were more sensitive to the combination of bortezomib with a BCL-XL selective inhibitor (A-1331852) but not with venetoclax cotreatment when compared with monotherapies.
2.Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy.
Leverson JD;Phillips DC;Mitten MJ;Boghaert ER;Diaz D;Tahir SK;Belmont LD;Nimmer P;Xiao Y;Ma XM;Lowes KN;Kovar P;Chen J;Jin S;Smith M;Xue J;Zhang H;Oleksijew A;Magoc TJ;Vaidya KS;Albert DH;Tarrant JM;La N;Wang L;Tao ZF;Wendt MD;Sampath D;Rosenberg SH;Tse C;Huang DC;Fairbrother WJ;Elmore SW;Souers AJ Sci Transl Med. 2015 Mar 18;7(279):279ra40. doi: 10.1126/scitranslmed.aaa4642.
The BCL-2/BCL-XL/BCL-W inhibitor ABT-263 (navitoclax) has shown promising clinical activity in lymphoid malignancies such as chronic lymphocytic leukemia. However, its efficacy in these settings is limited by thrombocytopenia caused by BCL-XL inhibition. This prompted the generation of the BCL-2-selective inhibitor venetoclax (ABT-199/GDC-0199), which demonstrates robust activity in these cancers but spares platelets. Navitoclax has also been shown to enhance the efficacy of docetaxel in preclinical models of solid tumors, but clinical use of this combination has been limited by neutropenia. We used venetoclax and the BCL-XL-selective inhibitors A-1155463 and A-1331852 to assess the relative contributions of inhibiting BCL-2 or BCL-XL to the efficacy and toxicity of the navitoclax-docetaxel combination. Selective BCL-2 inhibition suppressed granulopoiesis in vitro and in vivo, potentially accounting for the exacerbated neutropenia observed when navitoclax was combined with docetaxel clinically. By contrast, selectively inhibiting BCL-XL did not suppress granulopoiesis but was highly efficacious in combination with docetaxel when tested against a range of solid tumors. Therefore, BCL-XL-selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax.
3.Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations.
Henz K;Al-Zebeeby A;Basoglu M;Fulda S;Cohen GM;Varadarajan S;Vogler M Biol Chem. 2018 Jul 10. pii: /j/bchm.ahead-of-print/hsz-2018-0233/hsz-2018-0233.xml. doi: 10.1515/hsz-2018-0233. [Epub ahead of print]
Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Specifically, the selective BH3-mimetics ABT-199, A-1331852 and S63845, which target BCL-2, BCL-XL and MCL-1, respectively, induce comparable ultrastructural changes including mitochondrial swelling, a decrease of mitochondrial matrix density and severe loss of cristae structure. These shared effects on mitochondrial morphology indicate a similar function of these anti-apoptotic BCL-2 proteins in maintaining mitochondrial integrity and function.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Bcl-2 Family Products


CAS 1430844-80-6 A-1331852

A-1331852
(CAS: 1430844-80-6)

A-1331852, a substituted benzothiazole, is a high affinity BH3 mimetic Ligand of BCL protein BCL-XL (Ki≤ 10 pM). A-1331852 is an orally apoptosis-inducing agent...

CAS 1257044-40-8 venetoclax

venetoclax
(CAS: 1257044-40-8)

Venetoclax is a small-molecule inhibitor that has high selectivity for Bcl-2 (Ki < 0.01 nM in cell-free assays) over Mcl-1. It suppresses anti-apoptotic Bcl-2, ...

CAS 866541-93-7 AT-101 acetic acid

AT-101 acetic acid
(CAS: 866541-93-7)

AT101 acetic acid is orally bioavailable solvate of R-(-)-enantiomer of gossypol with potential antineoplastic activity. It is used as the treatment of non Hodg...

WEHI-539
(CAS: 1431866-33-9)

WEHI-539, a selective BCL-XL inhibitor that can be function as a single-agent inducer of apoptosis while sparing normal cells, it leads to MOMP and apoptosis du...

MIM1
(CAS: 509102-00-5)

MIM1 is a small molecule inhibitor of Mcl-1 (IC50= 4.8 uM) by selectively targets the BH3-binding pocket.

Pyridoclax
(CAS: 1651890-44-6)

Pyridoclax, a pyridine derivative, has been found to be a Mcl-1 inhibitor that could induce apoptosis of cancer cells. IC50: 25 nM(Kd).

S-63845
(CAS: 1799633-27-4)

S-63845 is a selective inhibitor of MCL1 (Ki (MCL1, FP) < 1.2 nM; Kd (MCL1, SPR) = 0.19 nM; Ki (BCL2, FP) > 10.000 1.2 nM; Ki (BCL-XL, FP) > 10.000 1.2 nM). It ...

CAS 579492-81-2 Bax inhibitor peptide V5

Bax inhibitor peptide V5
(CAS: 579492-81-2)

Bax inhibitor peptide V5, a peptide inhibitor, as a pro-apoptotic member of Bcl-2 family proteins and plays an important role in mitochondria-dependent apoptosi...

Mcl1-IN-2
(CAS: 292057-76-2)

Mcl1-IN-2, a hydroxyquinoline derivative, is an Mcl-1 inhibitor.

BDA 366
(CAS: 1821496-27-8)

BDA-366 is a BCL2-BH4 antagonist(Ki=3.3nM) which suppresses human myeloma growth. BDA-366 induces apoptosis in MM cell lines and primary MM cells by inducing BC...

CAS 329349-20-4 Bax channel blocker

Bax channel blocker
(CAS: 329349-20-4)

Bax channel blocker is a potent inhibitor of Bax-mediated mitochondrial cytochrome c release (IC50 = 0.52 μM).

BDA-366
(CAS: 1909226-00-1)

BDA-366 is a small-molecule antagonist of Bcl2-BH4 domain with high affinity and selectivity for Bcl2-BH4. BDA-366 induces apoptosis in multiple myeloma cells v...

CAS 1235034-55-5 A-1155463

A-1155463
(CAS: 1235034-55-5)

A-1155463, an effective and selective BCL-XL inhibitor, has been studied to have probable effect in restraining the growth of small cell lung cancer xenograft t...

A-1210477
(CAS: 1668553-26-1)

A-1210477 is a potent and selective MCL-1 inhibitor with Ki and IC50 of 0.454 nM and 26.2 nM, respectively, >100-fold selectivity over other Bcl-2 family member...

CAS 315698-17-0 ML311

ML311
(CAS: 315698-17-0)

ML311, also known as EU-5346, is a potent and selective inhibitor of the Protein-Protein Interaction of Mcl-1 and Bim. EU-5346 inhibits proliferation of Her2-po...

CAS 2752-65-0 Gambogic acid

Gambogic acid
(CAS: 2752-65-0)

Gambogic acid is a natural product inhibitor of Hsp90.

CAS 803712-79-0 Obatoclax mesylate

Obatoclax mesylate
(CAS: 803712-79-0)

Obatoclax mesylate is the mesylate salt of obatoclax, a synthetic small-molecule inhibitor of the bcl-2 family of proteins with potential pro-apoptotic and anti...

CAS 852808-04-9 ABT-737

ABT-737
(CAS: 852808-04-9)

ABT-737 is a potent, cell-permeable mimetic of BH3 domains that avidly binds Bcl-2, Bcl-xL, and Bcl-W (Ki < 1 nM for all three proteins). It blocks the interact...

CAS 12542-36-8 Gossypol Acetic Acid

Gossypol Acetic Acid
(CAS: 12542-36-8)

The Acetate acid salt form of gossypol which may represent a promising new anticancer agent with a novel molecular mechanism and warrants further investigation ...

CAS 923564-51-6 Navitoclax

Navitoclax
(CAS: 923564-51-6)

Navitoclax is an orally active, synthetic small molecule and an antagonist of a subset of the B-cell leukemia 2 (Bcl-2) family of proteins with potential antine...

Chemical Structure

CAS 1430844-80-6 A-1331852

Quick Inquiry

Verification code

Featured Items