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

General Information of Drug (ID: DM3WP0N)

• Drug Name: AL3818 Drug Info
• Synonyms: Anlotinib; 1058156-90-3; UNII-GKF8S4C432; GKF8S4C432; AL-3818; SCHEMBL2063386; GTPL9601; KSMZEXLVHXZPEF-UHFFFAOYSA-N; MolPort-044-567-604; ZINC117924202; AKOS030526233; DB11885; CS-5396; AL 3818; HY-19716; 1-[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinolin-7-yl]oxymethyl]cyclopropan-1-amine; 1-((4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropan-amine; Cyclopropanamine, 1-(((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-quinolinyl)oxy)methyl)-

Indication

Disease Entry	ICD 11	Status	REF
Alveolar soft part sarcoma	2A60-2C35	Phase 3	[1]
Leiomyosarcoma	2B58	Phase 3	[1]
Synovial sarcoma	2B5A	Phase 3	[1]
Cervical cancer	2C77.0	Phase 1/2	[1]
Endometrial cancer	2C76	Phase 1/2	[1]
Fallopian tube cancer	2C74	Phase 1/2	[1]
Ovarian cancer	2C73	Phase 1/2	[1]
Peritoneal cavity cancer	2C51.Z	Phase 1/2	[1]

• Cross-matching ID:
  PubChem CID: 25017411
  CAS Number: CAS 1058156-90-3
  TTD Drug ID: DM3WP0N
  INTEDE Drug ID: DR1881

Molecule-Related Drug Atlas

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[3]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[3]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[4]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[1]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[6]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[7]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[8]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[9]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[10]

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	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[20]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[21]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[27]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[28]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[2]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development. J Hematol Oncol. 2018 Sep 19;11(1):120.
• [3] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [4] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [5] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [9] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [10] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [11] 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.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] 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.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] 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.
• [16] 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.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] 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.
• [19] 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.
• [20] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [21] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [22] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [23] Drug Interactions Flockhart Table
• [24] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [25] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [26] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [27] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [28] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.