1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]-
![1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- Structure](CAS/20210305/GIF/1863952-15-1.gif)
- CAS No.
- 1863952-15-1
- Chemical Name:
- 1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]-
- Synonyms
- CB-5339;p97-IN-1;Dabigatran Impurity 127;1-(4-(benzylamino)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide;H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]-;1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]-
- CBNumber:
- CB09018534
- Molecular Formula:
- C24H24N6O
- Molecular Weight:
- 412.49
- MDL Number:
- MOL File:
- 1863952-15-1.mol
1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- Properties
| Boiling point | 751.8±70.0 °C(Predicted) |
|---|---|
| Density | 1.38±0.1 g/cm3(Predicted) |
| storage temp. | Store at -20°C |
| solubility | DMSO : 41.67 mg/mL |
| pka | 16.12±0.30(Predicted) |
| form | Solid |
| color | Off-white to yellow |
1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- Chemical Properties,Uses,Production
Biological Activity
CB-5339 is a second generation, potent and selective, orally bioavailable, ATP-competitive, small molecule inhibitor of valosin containing protein (VCP)/p97 [1,2]. CB-5339 is an ATP-competitive, small molecule inhibitor of p97 with IC50 of 53 nM [3]. CB-5339 effectively effect on a panel of 16 primary AML patient samples harboring diverse genetic backgrounds. The median IC50 value was 375 nM among these samples [1]. CB-5339 (200 to 1000 nM for 48 hours) induces in vitro loss of viability in AML cell lines (OCI-AML3, MOLM13, SET2 and HEL92.1.7 cells), as well as in fresh, patient-derived (PD) AML cells, including those with TP53 mutations and/or TP53 allelic loss, or with 3q26 (MECOM locus) lesions and EVI1 overexpression [2]. CB-5339 induced accumulation of polyubiquitylated proteins, retention of ERAD substrates, and lethal ER stress in cancer cells mediated by CHOP, DR5 and NOXA [2]. CB-5339 has higher bioavailability than CB-5083 [1]. Treatment with CB-5339 (90 mg/kg) reduced invasion of myeloid leukemia and prolonged survival in an MLL-AF9-driven PDX AML mouse model [1]. In a tail-vein infused, luciferase transduced, aggressive xenograft model of MOLM13 cells, after AML engraftment, co-treatment for 3 weeks with CB-5339 (50 mg/kg/day, PO) and either venetoclax (30 mg/kg/day, PO) or OTX015 (30 mg/kg/day, PO), as compared to treatment with vehicle or each drug alone, significantly reduced the AML burden and improved median and overall survival of the NSG mice, without inducing significant toxicity [2].
References
[1]. B Roux B, Vaganay C, Vargas J D, et al. Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor[J]. Science translational medicine, 2021, 13(587): eabg1168.[2]. Fiskus W C, Das K, Mill C P, et al. Efficacy of Vcp/p97 Inhibitor, CB-5339, Alone and in Combinations Against High-Risk AML, Including Those with Genetic Lesion in TP53[J]. Blood, 2022, 140(Supplement 1): 8807-8808.[3]. Wang X, Wen T, Miao H, et al. Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of colorectal cancer[J]. Bioorganic & Medicinal Chemistry, 2022, 74: 117050.
1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- Preparation Products And Raw materials
Raw materials
Preparation Products
1H-Indole-4-carboxamide, 2-methyl-1-[5,6,7,8-tetrahydro-4-[(phenylmethyl)amino]pyrido[2,3-d]pyrimidin-2-yl]- Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32951 | 60 |
| TargetMol Chemicals Inc. | +1-781-999-5354 +1-00000000000 | marketing@targetmol.com | United States | 32080 | 58 |
| Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 +1-2135480471 | sales@sarms4muscle.com | China | 10473 | 58 |
| China National Standard Pharmaceutical Corporation Limited | +8615391658522 | overseasales@yongstandards.com | China | 11922 | 58 |
| Chuzhou KeMail Chemical Technology Co., Ltd | 0550-5196001 15000891977 | wj520wjxby@126.com | China | 1847 | 55 |
| Guangzhou Isun Pharmaceutical Co., Ltd | 020-39119399 18927568969 | isunpharm@qq.com | China | 4428 | 55 |
| ShangHai Caerulum Pharma Discovery Co., Ltd. | 18149758185 18149758185 | sales-cpd@caerulumpharma.com | China | 3466 | 58 |
| ChemStrong Scientific Co.,Ltd | 0755-0755-66853366 13670046396 | sales@chem-strong.com | China | 18043 | 56 |
| Shanghai Kewel Chemical Co., Ltd. | 021-64609169 18901607656 | greensnown@163.com | China | 9906 | 50 |
| Shanghai Lollane Biological Technology Co.,Ltd. | 021-52996696，15000506266 15000506266 | China | 4512 | 55 |
