Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DML2D8Q)

• Drug Name: Bevirimat Drug Info
• Synonyms: DSB; Bevirimat dimeglumine; DSB 2NMG; MPC-4326; PA-457; PA-103001-01; PA-103001-04; PA-457 di-NMG; Viral maturation inhibitor (HIV), Myrexis; Viral maturation inhibitor (HIV), Myriad; Viral maturation inhibitor (HIV), Panacos; YK-FH-312; 3-O-(3' 3'-dimethylsuccinyl)-betulinic acid

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 457928
  ChEBI ID: CHEBI:65484
  CAS Number: CAS 174022-42-5
  TTD Drug ID: DML2D8Q
  INTEDE Drug ID: DR1856

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus GAG protein (HIV gag)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LIPO-5	DMWY0V1	Human immunodeficiency virus infection	1C62	Phase 2	[4]
Ad35-GRIN	DM4L28K	Human immunodeficiency virus infection	1C62	Phase 1/2	[5]
Ad35-GRIN/ENV	DMG82ZA	Human immunodeficiency virus infection	1C62	Phase 1	[5]
TBC-M4	DM9CDPO	Human immunodeficiency virus infection	1C62	Phase 1	[6]
RVSVIN HIV-1 gag vaccine	DMYRPC8	Human immunodeficiency virus infection	1C62	Phase 1	[7]
GSK-732461	DMJ0ZB6	Human immunodeficiency virus infection	1C62	Discontinued in Phase 2	[8]
PA-1050040	DMF4KPM	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[9]
Gem 92	DM4ZDVY	Human immunodeficiency virus-1 infection	1C62	Discontinued in Phase 1	[10]
MPC-9055	DMCMNKV	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[11]
MPI-461359	DMAVD4Q	Human immunodeficiency virus infection	1C62	Terminated	[12]

Drug(s) Metabolized By UDP-glucuronosyltransferase 2B7 (UGT2B7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[17]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[15]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[19]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[20]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[21]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A3 (UGT1A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[15]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[24]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[25]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[19]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[26]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[21]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[15]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A4 (UGT1A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lorlatinib	DMICDLV	Non-small-cell lung cancer	2C25.Y	Approved	[27]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[28]
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[29]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[30]
LM-94	DMW3QGJ	N. A.	N. A.	Phase 1/2	[31]
UDP-glucuronic acid	DMW16X2	Discovery agent	N.A.	Investigative	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus GAG protein (HIV gag)	TTFGZB6	GAG_HV1H2	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Substrate	[3]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Substrate	[3]
UDP-glucuronosyltransferase 1A4 (UGT1A4)	DELOY3P	UD14_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT00967187) Safety and Efficacy Study of MPC-4326 for Treatment of Patients With HIV-1 Infection.. U.S. National Institutes of Health.
• [2] Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site. Eur J Med Chem. 2013 Apr;62:453-65.
• [3] Bevirimat: a novel maturation inhibitor for the treatment of HIV-1 infection. Antivir Chem Chemother. 2008;19(3):107-13.
• [4] HIV specific responses induced in nonhuman primates with ANRS HIV-Lipo-5 vaccine combined with rMVA-HIV prime or boost immunizations. Vaccine. 2015 May 11;33(20):2354-9.
• [5] A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. PLoS One. 2012;7(8):e41936.
• [6] A Phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C-modified vaccinia Ankara virus vaccine candidate in Indian volunteers. AIDS Res Hum Retroviruses. 2009 Nov;25(11):1107-16.
• [7] Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections. J Infect Dis. 2011 Nov;204 Suppl 3:S1075-81.
• [8] Preventive technologies, research toward a cure, and immune-based and gene therapies. HIV Treatment Bulletin. 30 June 2013.
• [9] US patent application no. 2015,0105,350, Combination therapy comprising tenofovir alafenamide hemifumarate and cobicistat for use in the treatment of viral infections.
• [10] Technology evaluation: GEM-92, Hybridon Inc. Curr Opin Mol Ther. 1999 Aug;1(4):521-3.
• [11] New Small-Molecule Inhibitor Class Targeting Human Immunodeficiency Virus Type 1 Virion Maturation . Antimicrob Agents Chemother. 2009 December; 53(12): 5080-5087.
• [12] Human Immunodeficiency Virus Gag and protease: partners in resistance. Retrovirology. 2012 Aug 6;9:63.
• [13] Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
• [14] Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultra-performance liquid chromatography with MS detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):84-90.
• [15] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [16] Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
• [17] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [18] Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
• [19] Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
• [20] Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
• [21] Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
• [22] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
• [23] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [24] UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7.
• [25] Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
• [26] Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8.
• [27] FDA label of Lorlatinib. The 2020 official website of the U.S. Food and Drug Administration.
• [28] Studies on induction of lamotrigine metabolism in transgenic UGT1 mice. Xenobiotica. 2009 Nov;39(11):826-35.
• [29] Human biotransformation of the nonnucleoside reverse transcriptase inhibitor rilpivirine and a cross-species metabolism comparison. Antimicrob Agents Chemother. 2013 Oct;57(10):5067-79.
• [30] Identification of human UDP-glucuronosyltransferases catalyzing hepatic 1alpha,25-dihydroxyvitamin D3 conjugation. Biochem Pharmacol. 2008 Mar 1;75(5):1240-50.
• [31] Identification of aspartic acid and histidine residues mediating the reaction mechanism and the substrate specificity of the human UDP-glucuronosyltransferases 1A. J Biol Chem. 2007 Dec 14;282(50):36514-24.