Drug Details
| General Information of the Drug (ID: DR0618) | ||||
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| Name |
Carfilzomib
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| Synonyms |
Kyprolis; Carfilzomib (PR-171); PR-171; UNII-72X6E3J5AR; 72X6E3J5AR; CHEMBL451887; CHEBI:65347; NCGC00249613-01; DSSTox_RID_82886; DSSTox_CID_28616; DSSTox_GSID_48690; (S)-4-methyl-N-((S)-1-(((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)pentanamide; N-{(2S)-2-[(morpholin-4-ylacetyl)amino]-4-phenylbutanoyl}-L-leucyl-N-{(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl}-L-phenylalaninamide; 868540-17-4
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| Molecular Type |
Small molecule
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| Disease | Multiple myeloma [ICD-11: 2A83] | Approved | [1] | |
| Structure |
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Click to Download Mol2D MOL |
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | ||||
| Formula |
C40H57N5O7
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| PubChem CID | ||||
| Canonical SMILES |
CC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4
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| InChI |
1S/C40H57N5O7/c1-27(2)22-32(36(47)40(5)26-52-40)42-39(50)34(24-30-14-10-7-11-15-30)44-38(49)33(23-28(3)4)43-37(48)31(17-16-29-12-8-6-9-13-29)41-35(46)25-45-18-20-51-21-19-45/h6-15,27-28,31-34H,16-26H2,1-5H3,(H,41,46)(H,42,50)(H,43,48)(H,44,49)/t31-,32-,33-,34-,40+/m0/s1
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| InChIKey |
BLMPQMFVWMYDKT-NZTKNTHTSA-N
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| CAS Number |
CAS 868540-17-4
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| ChEBI ID | ||||
| TTD Drug ID | ||||
| DrugBank ID | ||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug | ||||||
| Curcumin | Hellenia speciosa | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | CDKN1A | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | NFKBIA | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TP53 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Induction | Cell cycle arrest in G0/G1 phase | ||||
| In-vitro Model | U266B1 | CVCL_0566 | Plasma cell myeloma | Homo sapiens | ||
| Experimental
Result(s) |
Curcumin significantly ameliorates CFZ cytotoxic effect. Induction of p53/p21 axis and G0/G1 cell cycle arrest were more pronounced for the CFZ-curcumin combination. | |||||
| Flavopiridol | Dysoxylum binectariferum | Click to Show/Hide the Molecular Data of This NP | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [3] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | XIAP | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Induction | Cell cycle arrest in G2/M phase | ||||
| In-vitro Model | NCI-H295R | CVCL_0458 | Adrenal cortex carcinoma | Homo sapiens | ||
| SW13 | CVCL_0542 | Adrenal cortex carcinoma | Homo sapiens | |||
| In-vivo Model | A total of 5*106 NCI-H295R cells with luciferase reporter were injected into each flank of a Nu/Nu mouse (two xenografts per mouse). | |||||
| Experimental
Result(s) |
Treatment with flavopiridol and carfilzomib in all three ACC cell lines resulted in a dose-dependent, anti-proliferative effect, and the combination had synergistic activity as well as in three-dimensional tumor spheroids. The combination treatment increased G2M cell-cycle arrest and apoptosis, and decreased XIAP protein expression in ACC cell lines. | |||||
| Target and Pathway | ||||
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| Target(s) | Proteasome (PS) | Molecule Info | [4] | |
