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], [2]
Small-cell lung cancer	2C25.Y	Phase 1/2	[3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

719.9

Topological Polar Surface Area (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 [4]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 4232 mcg/L [4]
Clearance: The sytemic clearance of drug is 151-263 L/h [5]
Half-life: The concentration or amount of drug in body reduced by one-half in less than 1 hour [6]
Metabolism: The drug is metabolized via the liver [4]
Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [6]
Vd: The volume of distribution (Vd) of drug is 28 L [5]

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

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proteasome (PS)	TTU7ZMG	NOUNIPROTAC	Modulator	[2]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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]	[22]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[23]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Carfilzomib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[24]
Esterified estrogens	DM9KZDO	Major	Additive thrombogenic effects by the combination of Carfilzomib and Esterified estrogens.	Breast cancer [2C60-2C6Y]	[22]
Levonorgestrel	DM1DP7T	Major	Additive thrombogenic effects by the combination of Carfilzomib and Levonorgestrel.	Contraceptive management [QA21]	[25]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Cannabidiol.	Epileptic encephalopathy [8A62]	[25]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[26]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Carfilzomib and Idelalisib.	Mature B-cell leukaemia [2A82]	[27]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Carfilzomib and Tecfidera.	Multiple sclerosis [8A40]	[28]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Carfilzomib and Siponimod.	Multiple sclerosis [8A40]	[22]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Carfilzomib and Ocrelizumab.	Multiple sclerosis [8A40]	[29]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Carfilzomib and Ozanimod.	Multiple sclerosis [8A40]	[25]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Carfilzomib when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[30]
Lusutrombopag	DMH6IKO	Major	Additive thrombogenic effects by the combination of Carfilzomib and Lusutrombopag.	Thrombocytopenia [3B64]	[22]
As-1670542	DMV05SW	Major	Additive thrombogenic effects by the combination of Carfilzomib and As-1670542.	Thrombocytopenia [3B64]	[22]
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⏷ Show the Full List of 15 DDI Information of This Drug

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	Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
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6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	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.
8	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
9	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
10	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
11	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
12	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
13	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
14	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
15	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16	Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80.
17	Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011 Mar;11(3):254-84.
18	A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010 Dec 2;116(23):4906-15.
19	Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE. Int Immunopharmacol. 2012 Jan;12(1):257-70.
20	Effect of the proteasome inhibitor MLN519 on the expression of inflammatory molecules following middle cerebral artery occlusion and reperfusion in... Neurotox Res. 2003;5(7):505-14.
21	Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study.J Mol Model.2009 Dec;15(12):1481-90.
22	Cerner Multum, Inc. "Australian Product Information.".
23	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
24	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
25	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
26	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]
27	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
28	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
29	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
30	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]