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

General Information of Drug (ID: DM2CT4G)

• Drug Name: PMID25726713-Compound-49 Drug Info
• Cross-matching ID: TTD Drug ID: DM2CT4G

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	[2]
Vismodegib	DM5IXKQ	Basal cell carcinoma	2C32	Approved	[3]
LDE225	DMM9F25	Basal cell carcinoma	2C32	Phase 2	[4]
LY2940680	DMTJWIQ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
BMS-833923	DM459Q7	Solid tumour/cancer	2A00-2F9Z	Phase 1b	[5]
LEQ-506	DM5INZP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
TAK-441	DM7DFBL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
PMID25726713-Compound-51	DMF0OW4	N. A.	N. A.	Patented	[1]
PMID25726713-Compound-48	DMSIOUA	N. A.	N. A.	Patented	[1]
PMID25726713-Compound-47	DMXE5KM	N. A.	N. A.	Patented	[1]

Drug(s) Targeting Serine/threonine-protein kinase mTOR (mTOR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[8]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[9]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[10]
Everolimus	DM8X2EH	Advanced cancer	2A00-2F9Z	Approved	[11]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[12]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[14]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[16]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[12]

Drug(s) Targeting Cyclin-dependent kinase 4 (CDK4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[17]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[2]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[18]
Ribociclib Succinate	DM9CIUW	Breast cancer	2C60-2C65	Approved	[19]
Trilaciclib	DMP5A4T	Small-cell lung cancer	2C25.Y	Approved	[20]
LEE011	DMMX75K	Breast cancer	2C60-2C65	Phase 3	[21]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[23]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[24]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[16]

Drug(s) Targeting Cyclin-dependent kinase 6 (CDK6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[17]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[2]
Palbociclib	DMD7L94	Breast cancer	2C60-2C65	Approved	[18]
Ribociclib Succinate	DM9CIUW	Breast cancer	2C60-2C65	Approved	[19]
Trilaciclib	DMP5A4T	Small-cell lung cancer	2C25.Y	Approved	[20]
LEE011	DMMX75K	Breast cancer	2C60-2C65	Phase 3	[21]
G1T38	DMQO2IT	Breast cancer	2C60-2C65	Phase 2	[16]
GLR2007	DM7DWLY	Glioblastoma of brain	2A00.00	Phase 1/2	[25]
FCN-437	DMQ8VUW	Breast cancer	2C60-2C65	Phase 1/2	[26]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Inhibitor	[1]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[1]
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Inhibitor	[1]

References

• [1] Hedgehog inhibitors: a patent review (2013 - present).Expert Opin Ther Pat. 2015 May;25(5):549-65.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [4] 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.
• [5] Clinical pipeline report, company report or official report of Exelixis (2011).
• [6] Discovery of NVP-LEQ506, a second-generation inhibitor of smoothened. ChemMedChem. 2013 Aug;8(8):1261-5.
• [7] 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.
• [8] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [9] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
• [12] 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. (Target id: 2109).
• [13] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [14] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [15] Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [21] Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
• [22] 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.
• [23] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [24] Liposarcoma: molecular genetics and therapeutics. Sarcoma. 2011;2011:483154.
• [25] Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.
• [26] Clinical pipeline report, company report or official report of Fochon Pharmaceuticals.
• [27] ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.