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

General Information of Drug (ID: DMBL3VD)

• Drug Name: PF-05212384 Drug Info
• Synonyms: PKI-587; 1197160-78-3; Gedatolisib; PF-05212384; PKI587; PKI 587; 1-(4-(4-(Dimethylamino)piperidine-1-carbonyl)phenyl)-3-(4-(4,6-dimorpholino-1,3,5-triazin-2-yl)phenyl)urea; PF 05212384; UNII-96265TNH2R; PF-05212384 (PKI-587); CHEMBL592445; 96265TNH2R; N-[4-[[4-(Dimethylamino)-1-piperidinyl]carbonyl]phenyl]-N'-[4-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]phenyl]urea; Gedatolisib (PF-05212384, PKI-587); Urea, N-(4-((4-(dimethylamino)-1-piperidinyl)carbonyl)phenyl)-N'-(4-(4,6-di-4-morpholinyl-1,3,5-triazin-2-yl)phenyl)-

Indication

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

• Cross-matching ID:
  PubChem CID: 44516953
  CAS Number: CAS 1197160-78-3
  TTD Drug ID: DMBL3VD

Molecule-Related Drug Atlas

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	[3]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[4]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[5]
Everolimus	DM8X2EH	Advanced cancer	2A00-2F9Z	Approved	[6]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[7]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[9]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[11]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[7]

Drug(s) Targeting PI3-kinase gamma (PIK3CG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[12]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[13]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[14]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[11]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[15]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[11]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[16]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[2]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Modulator	[2]

References

• [1] 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. (Ligand id: 7940).
• [2] First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
• [3] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [4] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] 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.
• [7] 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).
• [8] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [9] 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.
• [10] 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.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
• [13] PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
• [14] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [15] Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
• [16] 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: 2155).
• [17] 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: 2156).
• [18] An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.