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

General Information of Drug (ID: DMTJWIQ)

• Drug Name: LY2940680 Drug Info
• Synonyms: LY2940680; 1258861-20-9; Taladegib; LY-2940680; UNII-QY8BWX1LJ5; 4-Fluoro-N-methyl-N-(1-(4-(1-methyl-1H-pyrazol-5-yl)phthalazin-1-yl)piperidin-4-yl)-2-(trifluoromethyl)benzamide; QY8BWX1LJ5; Taladegib (LY2940680); LY 2940680; 4-fluoro-n-methyl-n-(1-(4-(1-methyl-1h-pyrazol-5-yl)-1-phthalazinyl)-4-piperidinyl)-2-(trifluoromethyl)benzamide; 4-Fluoro-N-Methyl-N-{1-[4-(1-Methyl-1h-Pyrazol-5-Yl)phthalazin-1-Yl]piperidin-4-Yl}-2-(Trifluoromethyl)benzamide; Taladegib [USAN:INN]

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]
Ovarian cancer	2C73	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 49848070
  CAS Number: CAS 1258861-20-9
  TTD Drug ID: DMTJWIQ
  INTEDE Drug ID: DR1816

Molecule-Related Drug Atlas

Drug(s) Targeting Smoothened homolog (SMO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[3]
Vismodegib	DM5IXKQ	Basal cell carcinoma	2C32	Approved	[5]
LDE225	DMM9F25	Basal cell carcinoma	2C32	Phase 2	[6]
BMS-833923	DM459Q7	Solid tumour/cancer	2A00-2F9Z	Phase 1b	[7]
LEQ-506	DM5INZP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
TAK-441	DM7DFBL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
PMID25726713-Compound-49	DM2CT4G	N. A.	N. A.	Patented	[10]
PMID25726713-Compound-51	DMF0OW4	N. A.	N. A.	Patented	[10]
PMID25726713-Compound-48	DMSIOUA	N. A.	N. A.	Patented	[10]
PMID25726713-Compound-47	DMXE5KM	N. A.	N. A.	Patented	[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]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

• [1] ClinicalTrials.gov (NCT01722292) A Study of LY2940680 in Small Cell Lung Cancer. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [4] Phase I study of LY2940680, a Smo antagonist, in patients with advanced cancer including treatment-naive and previously treated basal cell carcinoma. Clin Cancer Res. 2018 May 1;24(9):2082-2091.
• [5] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [6] Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells. Br J Cancer. 2014 Sep 9;111(6):1168-79.
• [7] Clinical pipeline report, company report or official report of Exelixis (2011).
• [8] Discovery of NVP-LEQ506, a second-generation inhibitor of smoothened. ChemMedChem. 2013 Aug;8(8):1261-5.
• [9] TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. Int J Cancer. 2013 Oct 15;133(8):1955-66.
• [10] Hedgehog inhibitors: a patent review (2013 - present).Expert Opin Ther Pat. 2015 May;25(5):549-65.
• [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.