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| Product Name: | CB5083 | | Synonyms: | CB5083;CB-5083;1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carboxamide;EOS-61078;CB 5083;CB5083;CS-1553;1-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methylindole-4-carboxamide;1-[4-(benzylamino)-5H,7H,8H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-1H-indole-4-carboxamide | | CAS: | 1542705-92-9 | | MF: | C24H23N5O2 | | MW: | 413.47 | | EINECS: | | | Product Categories: | | | Mol File: | 1542705-92-9.mol |  |
| | CB5083 Chemical Properties |
| Boiling point | 760.5±70.0 °C(Predicted) | | density | 1.37±0.1 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | insoluble in H2O; ≥20.65 mg/mL in DMSO; ≥4.4 mg/mL in EtOH | | form | solid | | pka | 15.99±0.30(Predicted) |
| | CB5083 Usage And Synthesis |
| Biological Activity | cb-5083 is an orally bioavailable inhibitor of p97. p97 is an aaa-atpase involved in multiple cellular functions such as organelle membrane homotypic fusion and sorting of endosomal cargo. p97 is also known as valosin-containing protein which plays important roles in regulating protein homeostasis [1]. | | in vitro | cb-5083 is a selective potent inhibitor of p97’s second atpase domain. cb-5083 might compete with atp for the same binding site but may adopt a different orientation[2]. the ic50 of cb-5083 against wild-type (wt) p97 was 15.4 nm. cb-5083 could dose-dependently increase the cytosolic protein degradation in hek293t, a549 and hct116 cell lines [1]. cb-5083 treatment (2.5 μm) of a549 cells for 24h could induce cancer cell death [1]. | | in vivo | in female nude mice bearing hct116, a549 lung carcinoma, and amo-1 multiple myeloma xenograft tumors, oral administration of cb-5083 (100 mg/kg) for 6 h showed a significant antitumor response in tumors (tgi = 63%, p < 0.0001) [1,2]. | | IC 50 | 15.4 nm | | storage | Store at -20°C | | references | anderson d j, le moigne r, djakovic s, et al. targeting the aaa atpase p97 as an approach to treat cancer through disruption of protein homeostasis[j]. cancer cell, 2015, 28(5): 653-665.zhou h j, wang j, yao b, et al. discovery of a first-in-class, potent, selective, and orally bioavailable inhibitor of the p97 aaa atpase (cb-5083)[j]. journal of medicinal chemistry, 2015, 58(24): 9480-9497. |
| | CB5083 Preparation Products And Raw materials |
| Raw materials | 1-(4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)-2-methyl-1H-indole-4-carbonitrile-->4-Cyano-2-Methyl-1H-indole-->N-benzyl-2-chloro-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine-->METHYL 4-AMINO-5,6-DIHYDRO-2H-PYRAN-3-CARBOXYLATE-->2,4-Dichloro-7,8-dihydro-5H-pyrano[4,3-d]pyriMidine-->7,8-dihydro-5H-pyrano[4,3-d]pyrimidine-2,4-diol-->Methyl 4-oxotetrahydro-2H-pyran-3-carboxylate-->4-Cyanoindole-->Acetaldoxime-->Tetrahydro-4H-pyran-4-one |
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