| Identification | Back Directory | [Name]
A-1331852 | [CAS]
1430844-80-6 | [Synonyms]
CS-2498
A-1331852
A 1331852;A1331852
6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-(adamantylmethyl)-5-methyl-1H-pyrazol-4-yl)picolinic acid
6-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl]-3-[5-methyl-1-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-1H-pyrazol-4-yl]pyridine-2-carboxylic acid
2-Pyridinecarboxylic acid, 6-[8-[(2-benzothiazolylamino)carbonyl]-3,4-dihydro-2(1H)-isoquinolinyl]-3-[5-methyl-1-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-1H-pyrazol-4-yl]- | [Molecular Formula]
C38H38N6O3S | [MDL Number]
MFCD30532662 | [MOL File]
1430844-80-6.mol | [Molecular Weight]
658.81 |
| Chemical Properties | Back Directory | [Melting point ]
>161oC (dec.) | [density ]
1.50±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
Acetonitrile (Slightly, Heated), DMSO (Slightly) | [form ]
Solid | [pka]
8.88±0.70(Predicted) | [color ]
Pale Yellow to Light Beige |
| Hazard Information | Back Directory | [Description]
A-1331852 is an orally bioavailable Bcl-xL inhibitor that selectively binds Bcl-xL over Bcl-2, Mcl-1, and Bcl-W (Kis = <0.01, 6, 142, and 4 nM, respectively).1 It inhibits growth of Bcl-xL-dependent MOLT-4, but not Bcl-2-dependent RS4;11, acute lymphocytic leukemia cells in vitro (EC50s = 6 and >5,000 nM, respectively). A-1331852 (25 mg/kg twice per day) inhibits tumor growth in a MOLT-4 mouse xenograft model. It also inhibits tumor growth and increases the antitumor activity of docetaxel (Item No. 11637) in MDA-MB-231 LC3 metastatic breast cancer and NCI-H1650 non-small cell lung cancer mouse xenograft models when administered at a dose of 25 mg/kg. A-1331852 also increases venetoclax inhibition of tumor growth in an NCI-H1963.FP5 small cell lung cancer mouse xenograft model. | [Uses]
A-1331852 is a substituted benzothiazole that can serve as an anti-apoptotic Bcl-xL protein inhibitor and apoptosis-inducing agent useful in the treatment of cancer, immune and autoimmune diseases. | [in vitro]
a-1331852 was identified as a potent bcl-xl inhibitor demonstrating cellular activity 10- to 50-fold more potent than its analog a-1155463 and the previouly reported bcl-xl inhibitor, navitoclax, respectively. moreover, a-1331852 could selectively disrupt bcl-xl–bim complexes and induce the apoptosis hallmarks in bcl-xl–dependent molt-4 cells with median ic50 values in the low nanomolar range but did not affect mef cells without bak or bax [1]. | [in vivo]
previous animal study found that a-1331852 could demonstrate antitumor efficacy in the molt-4 xenograft model, such as tumor regressions as a single agent. in addition, in the nci-h1963.fp5 xenograft model of sclc, it was found that a-1331852 combined with venetoclax was able to recapitulate the efficacy of navitoclax [1]. | [storage]
Store at -20°C | [References]
[1] leverson jd et al. exploiting selective bcl-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. sci transl med. 2015 mar 18;7(279):279ra40. doi: 10.1126/scitranslmed.aaa4642. |
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| Company Name: |
Cool Pharm, Ltd
|
| Tel: |
021-60455363 18019463053 |
| Website: |
www.coolpharm.com |
|