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

General Information of Drug (ID: DMMCYZ8)

• Drug Name: PQR309 Drug Info
• Synonyms: Bimiralisib; PQR309; 1225037-39-7; PI3K-IN-2; PQR-309; UNII-6Z3QHB00LB; 6Z3QHB00LB; 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine; 5-[bis(morpholin-4-yl)-1,3,5-triazin-2-yl]-4-(trifluoromethyl)pyridin-2-amine; 5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine; Bimiralisib [INN]; Bimiralisib [USAN]; PQR309; Bimiralisib; Bimiralisib [WHO-DD]; NCB5; SCHEMBL1309049; GTPL8383; PQR309; Bimiralisib free base; ADGGYDAFIHSYFI-UHFFFAOYSA-N; EX-A2018; BCP15887; PQR-309(PI3K-IN-2)

Indication

Disease Entry	ICD 11	Status	REF
Squamous head and neck cell carcinom	2D60.0	Phase 2	[1]
Pain	MG30-MG3Z	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 58507717
  CAS Number: CAS 1225037-39-7
  TTD Drug ID: DMMCYZ8

Molecule-Related Drug Atlas

Drug(s) Targeting PI3-kinase beta (PIK3CB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[6]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[7]
AZD8186	DMWYF1H	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
GSK2636771	DMCBGLW	Prostate cancer	2C82.0	Phase 1	[9]
BAY 1082439	DMLRGX1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
AZD6482	DMVP4E5	Thrombosis	DB61-GB90	Terminated	[11]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[12]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[13]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[14]
PI-3065	DMCQUWI	Discovery agent	N.A.	Investigative	[15]

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	[16]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[17]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[18]
Everolimus	DM8X2EH	Advanced cancer	2A00-2F9Z	Approved	[19]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[5]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[20]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[21]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[23]
Salirasib	DMRSU4X	Lung cancer	2C25.0	Phase 2	[5]

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	[24]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[25]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[6]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[23]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[26]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[23]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[27]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[27]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[28]
PF-05212384	DMBL3VD	Solid tumour/cancer	2A00-2F9Z	Phase 2	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase beta (PIK3CB)	TTTHBCA	PK3CB_HUMAN	Inhibitor	[3]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Inhibitor	[4]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[5]

References

• [1] ClinicalTrials.gov (NCT03740100) Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 Loss of Function Mutations (HNSCC). U.S. National Institutes of Health.
• [2] 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: 8383).
• [3] 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: 2154).
• [4] 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).
• [5] 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).
• [6] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [7] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [8] National Cancer Institute Drug Dictionary (drug id 751594).
• [9] 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: 7967).
• [10] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [11] Human target validation of phosphoinositide 3-kinase (PI3K)beta: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kbeta inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36.
• [12] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [13] Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors. Bioorg Med Chem. 2007 Sep 1;15(17):5837-44.
• [14] 1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed with dual DNA-PK/PI3-K inhibitory activity. J Med Chem. 2013 Aug 22;56(16):6386-401.
• [15] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.
• [16] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [17] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [18] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [19] 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.
• [20] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [21] 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.
• [22] 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.
• [23] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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).
• [28] 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.
• [29] 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.