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

General Information of Drug (ID: DMQZ5HF)

• Drug Name: KNI-272 Drug Info
• Synonyms: NSC651714; NSC-651714; AC1Q5L2H; (4r)-n-tert-butyl-3-[2-hydroxy-3-({n-[(isoquinolin-5-yloxy)acetyl]-s-methyl-l-cysteinyl}amino)-4-phenylbutanoyl]-1,3-thiazolidine-4-carboxamide; AC1L88B1; KNI 272; 3-(3,4-Dimethoxyphenyl)propionamide; NCI60_018063; 4-Thiazolidinecarboxamide,1-dimethylethyl)-3- [2-hydroxy-3-[[2-[[(5-isoquinolinyloxy)acetyl]amino]-3- (methylthio)-1-oxopropyl]amino]-1-oxo-4-phenylbutyl]-,[4R-[3[2S*,3S*(R*)],4R*]]

Indication

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

• Cross-matching ID:
  PubChem CID: 60927
  ChEBI ID: CHEBI:80006
  CAS Number: CAS 147318-81-8
  TTD Drug ID: DMQZ5HF
  INTEDE Drug ID: DR1857

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Protease (HIV PR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[4]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[5]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[6]
Atazanavir	DMSYRBX	Human immunodeficiency virus infection	1C62	Approved	[7]
Amprenavir	DMLMXE0	Human immunodeficiency virus infection	1C62	Approved	[8]
Darunavir	DMN3GCH	Human immunodeficiency virus infection	1C62	Approved	[9]
Tipranavir	DM8HJX6	Human immunodeficiency virus infection	1C62	Approved	[10]
Fosamprenavir	DM4W9B3	Human immunodeficiency virus infection	1C62	Approved	[11]
BI 201335	DM3MXT8	Hepatitis C virus infection	1E51.1	Phase 3	[12]
BMS 650032	DMQI43G	Hepatitis C virus infection	1E51.1	Phase 2	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Protease (HIV PR)	TT5FNQT	POL_HV1B1	Modulator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

References

• [1] Metabolic Characterization of a Tripeptide Human Immunodeficiency Virus Type 1 Protease Inhibitor, KNI-272, in Rat Liver Microsomes. Antimicrob Agents Chemother. 1999 March; 43(3): 549-556.
• [2] Oxidative modifications of kynostatin-272, a potent human immunodeficiency virus type 1 protease inhibitor: potential mechanism for altered activit... Antimicrob Agents Chemother. 2002 Feb;46(2):402-8.
• [3] Metabolic characterization of a tripeptide human immunodeficiency virus type 1 protease inhibitor, KNI-272, in rat liver microsomes. Antimicrob Agents Chemother. 1999 Mar;43(3):549-56.
• [4] PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63.
• [5] Quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cell lysate using liq... J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Feb 15;877(5-6):575-80.
• [6] Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20.
• [7] Hollow-fiber unit evaluation of a new human immunodeficiency virus type 1 protease inhibitor, BMS-232632, for determination of the linked pharmacod... J Infect Dis. 2001 Apr 1;183(7):1126-9.
• [8] Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503.
• [9] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] Fosamprenavir/ritonavir in advanced HIV disease (TRIAD): a randomized study of high-dose, dual-boosted or standard dose fosamprenavir/ritonavir in ... J Antimicrob Chemother. 2009 Aug;64(2):398-410.
• [12] 2011 Pipeline of Boehringer Ingelheim Pharma.
• [13] 2011 Pipeline of Bristol-Myers Squibb.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [19] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [22] 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.