(2S)-2-hydroxybutanedioic acid
cabozantinib (S)-malate
CAS: 1140909-48-3
Molecular Formula: C32H30FN3O10
(2S)-2-hydroxybutanedioic acid - Names and Identifiers
| Name | cabozantinib (S)-malate |
| Synonyms | Smalate XL184(S)-malate Carbozanitinb Malate cabozantinib (S)-malate Cabozantinib (XL184) S-malate Cabozantinib L-(-)-Apple Acid (2S)-2-hydroxybutanedioic acid N1-[4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl]-N1'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide,(2S)-2-hydroxybutanedioic acid N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide mono[(2S)-2-hydroxybutanedioate] |
| CAS | 1140909-48-3 |
| EINECS | 691-711-0 |
| InChI | InChI=1S/C28H24FN3O5.C4H6O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18;5-2(4(8)9)1-3(6)7/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34);2,5H,1H2,(H,6,7)(H,8,9)/t;2-/m.0/s1 |
(2S)-2-hydroxybutanedioic acid - Physico-chemical Properties
| Molecular Formula | C32H30FN3O10 |
| Molar Mass | 635.6 |
| Melting Point | 166-169°C |
| Solubility | DMSO 127 mg/mL Water <1 mg/mL Ethanol <1 mg/mL |
| Appearance | Solid |
| Color | White to Off-White |
| Storage Condition | Sealed in dry,Room Temperature |
| MDL | MFCD20923480 |
| In vitro study | Cabozantinib had weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectively, and weak activity against FGFR1 with IC50 of 5.294 μm. Cabozantinib at low concentrations (0.1-0.5 μm) is sufficient to significantly inhibit the production of constitutive and inducible Met phosphorylation and its resulting downstream signal in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. Cabozantinib also significantly inhibited Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). While Cabozantinib had no significant effect on MPNST cell growth at 0.1 μm, it significantly inhibited MPNST cell growth at 5-10 μm. |
| In vivo study | In RIP-Tag2 mice with spontaneous islet tumors, treatment with Cabozantinib at a dose of 30 mg/kg destroyed 83% of tumor vessels, reduced pericytes and empty basement membrane cuff, causing extensive intratumoral hypoxia and massive cancer cell apoptosis, and regrowth of tumor blood vessels after drug withdrawal, compared with XL999, more significantly blocked VEGFR without blocking c-Met, this resulted in only a 43% reduction in vascularity, suggesting that concurrent inhibition of VEGFR and other functionally related receptor tyrosine kinases (RTK) amplify the inhibition of angiogenesis. Cabozantinib also reduces primary tumor invasion and reduces metastasis. In SCID mice, Cabozantinib significantly abolished growth and metastasis of human MPNST xenografts at 30 mg/kg/day. Cabozantinib administration dose-dependently inhibits tumor growth in breast, lung, and glioma tumor models, which is associated with decreased tumor and endothelial cell proliferation and increased apoptosis. Single oral doses of Cabozantinib at 100 mg/kg and 10 mg/kg were sufficient to induce sustained tumor growth inhibition in MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats, respectively. |
(2S)-2-hydroxybutanedioic acid - Introduction
Cabozantinib malate (XL184), a Cabozantinib malate, is a potent VEGFR2 inhibitor with IC50 of 0.035 nM, also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2 and AXL,IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.
Last Update：2022-10-16 17:12:20
(2S)-2-hydroxybutanedioic acid - Reference Information
| use | carbotinib malate is a small molecule C- Met regulator. Carbotinib malate can be used as effective multi-target VEGFR2,Met,FLT3,Tie2,Kit and Ret inhibitors. IC50 for VEGFR2,Met,FLT3,Tie2 and Kit are 0.035, 1.8, 14.4, 14.3 and 4.6 nM respectively. Cabozantinib malate showed dose-dependent inhibition of tumor growth and tumor regression, which is related to the destruction of tumor vasculature and extensive tumor cell apoptosis. |
| Effect | Cabotinib malate was developed by Exelixis Biopharmaceutical Company in the United States. MET and VEGFR2 tyrosine kinases, which are mainly related to the growth and spread of prostate cancer, are used as targets to inhibit tumor metastasis and angiogenesis. |
| Synthesis | Using methyl 2-amino-4, 5-dimethoxybenzoate as the raw material, it is cyclized and chlorinated in turn to obtain 4-Chloro -6, 7-dimethoxyquinoline, and then nucleophilic substitution with p-aminophenol to obtain 6, 7-Dimethoxy -4-(4-aminophenoxy) quinoline (5) (or first react with p-nitrophenol, and then reduce with palladium to obtain 5),5 and cyclopropane -1,1-After the condensation of dicarboxylic acid, it reacts with p-fluoroaniline to prepare carbozinib, and finally with (S)-malic acid (8) to form a salt to obtain 1, lower overall yield (<20% ) |
| pharmacological effects | carbotinib malate (Cabozantinib S-MALATE), formerly known as XL184, was developed by Exelixis biopharmaceutical company in the United States. MET and VEGFR2 tyrosine kinases, which are mainly related to the growth and spread of prostate cancer, are used as targets to inhibit tumor metastasis and angiogenesis. carbotinib malate is a Cabozantinib malate and an effective VEGFR2 inhibitor. IC50 is 0.035 nM, and it also inhibits c-Met,Ret,Kit,Flt-1/3/4,Tie2 and AXL,IC50 is 1.3nM,4nM,4.6nM,12nM/11.3nM/6nM, 14.3nM and 7nM, respectively. |
| biological activity | Cabozantinib malate (XL184) is a Cabozantinib malate and an effective VEGFR2 inhibitor. IC50 is 0.035 nM, which also inhibits c-Met, RET (c-RET), Kit (c-Kit), Flt-1/3/4, Tie2 and AXL. IC50 in cell-free test is 1.3 nM and 4 nM respectively, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM. Cabozantinib malate (XL184) can induce apoptosis. |
| Target | Value |
| VEGFR2/KDR (Cell-free assay) | 0.035 nM |
| c-Met (Cell-free assay) | 1.3 nM |
| RET (Cell-free assay) | 4 nM |
| Kit (Cell-free assay) | 4.6 nM |
| Flt-4 (Cell-free assay) | 6 nM |
Last Update：2024-04-09 19:05:09
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