Details of the Drug

General Information of Drug (ID: DM48K0X)

Drug Name

Carfilzomib

Synonyms

Carfilzomib; 868540-17-4; 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

Indication

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Approved	[1]
Plasma cell myeloma	2A83.1	Approved	[2]
Small-cell lung cancer	2C25.Y	Phase 1/2	[3]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

719.9

Logarithm of the Partition Coefficient (xlogp)

4.7

Rotatable Bond Count (rotbonds)

20

Hydrogen Bond Donor Count (hbonddonor)

4

Hydrogen Bond Acceptor Count (hbondacc)

8

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 379 mcgh/L []
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 4232 mcg/L []
Clearance: The sytemic clearance of drug is 151-263 L/h []
Half-life: The concentration or amount of drug in body reduced by one-half in less than 1 hour [4]
Metabolism: The drug is metabolized via the liver []
Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [4]
Vd: The volume of distribution (Vd) of drug is 28 L []

Chemical Identifiers

Formula: C40H57N5O7
IUPAC Name: (2S)-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide
Canonical SMILES: CC(C)C[C@@H](C(=O)[C@]1(CO1)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC3=CC=CC=C3)NC(=O)CN4CCOCC4
InChI: 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
InChIKey: BLMPQMFVWMYDKT-NZTKNTHTSA-N

Cross-matching ID

PubChem CID: 11556711
ChEBI ID: CHEBI:65347
CAS Number: 868540-17-4
DrugBank ID: DB08889
TTD ID: D00UVA
VARIDT ID: DR01324
ACDINA ID: D00915

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proteasome (PS)	TTU7ZMG	NOUNIPROTAC	Modulator	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
AN1-type zinc finger protein 2A	OTTG7P8R	ZFN2A_HUMAN	Gene/Protein Processing	[7]
Basigin (BSG)	OTD0CVEC	BASI_HUMAN	Gene/Protein Processing	[8]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Drug Response	[9]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Gene/Protein Processing	[8]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Protein Interaction/Cellular Processes	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[10]
Cytochrome c oxidase subunit 8A, mitochondrial (COX8A)	OTU0NR39	COX8A_HUMAN	Gene/Protein Processing	[10]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Gene/Protein Processing	[10]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Gene/Protein Processing	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Carfilzomib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[12]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[13]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Carfilzomib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[14]
Esterified estrogens	DM9KZDO	Major	Additive thrombogenic effects by the combination of Carfilzomib and Esterified estrogens.	Breast cancer [2C60-2C6Y]	[12]
Levonorgestrel	DM1DP7T	Major	Additive thrombogenic effects by the combination of Carfilzomib and Levonorgestrel.	Contraceptive management [QA21]	[15]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Cannabidiol.	Epileptic encephalopathy [8A62]	[15]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[16]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Idelalisib.	Mature B-cell leukaemia [2A82]	[17]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Carfilzomib and Tecfidera.	Multiple sclerosis [8A40]	[18]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Carfilzomib and Siponimod.	Multiple sclerosis [8A40]	[12]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Carfilzomib and Ocrelizumab.	Multiple sclerosis [8A40]	[19]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Carfilzomib and Ozanimod.	Multiple sclerosis [8A40]	[15]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Carfilzomib when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[20]
Lusutrombopag	DMH6IKO	Major	Additive thrombogenic effects by the combination of Carfilzomib and Lusutrombopag.	Thrombocytopenia [3B64]	[12]
As-1670542	DMV05SW	Major	Additive thrombogenic effects by the combination of Carfilzomib and As-1670542.	Thrombocytopenia [3B64]	[12]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Kyselina citronova	E00014	311	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Betadex sulfobutyl ether sodium	E00589	66577045	Solubilizing agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Carfilzomib 60mg/vial powder	60mg/vial	Powder	Intravenous
Carfilzomib 30mg/vial powder	30mg/vial	Powder	Intravenous
Carfilzomib 10mg/vial powder	10mg/vial	Powder	Intravenous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7420).
2	Carfilzomib FDA Label
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
6	Identification of an ABCB1 (P-glycoprotein)-positive carfilzomib-resistant myeloma subpopulation by the pluripotent stem cell fluorescent dye CDy1. Am J Hematol. 2013 Apr;88(4):265-72.
7	The Zinc-Finger AN1-Type Domain 2a Gene Acts as a Regulator of Cell Survival in Human Melanoma: Role of E3-Ligase cIAP2. Mol Cancer Res. 2019 Dec;17(12):2444-2456. doi: 10.1158/1541-7786.MCR-19-0243. Epub 2019 Sep 20.
8	Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
9	Suppression of BRCA1 sensitizes cells to proteasome inhibitors. Cell Death Dis. 2014 Dec 18;5(12):e1580. doi: 10.1038/cddis.2014.537.
10	Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019 Feb 27;24(5):841. doi: 10.3390/molecules24050841.
11	Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
12	Cerner Multum, Inc. "Australian Product Information.".
13	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
14	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
15	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
16	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
17	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
18	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
19	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
20	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]