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

General Information of Drug (ID: DMLSYJQ)

• Drug Name: PA-799 Drug Info
• Synonyms: MEN1611; CH-5033855; CH-5061565; CH-5089788; CH-5108135; CH-5111436; CH-5138134

Indication

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 1/2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 49784945
  CAS Number: CAS 1007207-67-1
  TTD Drug ID: DMLSYJQ

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	[5]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[6]
AZD8186	DMWYF1H	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
GSK2636771	DMCBGLW	Prostate cancer	2C82.0	Phase 1	[8]
BAY 1082439	DMLRGX1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
AZD6482	DMVP4E5	Thrombosis	DB61-GB90	Terminated	[10]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[11]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[12]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[13]
PI-3065	DMCQUWI	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting PI3-kinase delta (PIK3CD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[15]
Idelalisib	DM602WT	Chronic lymphocytic leukaemia	2A82.0	Approved	[16]
Umbralisib	DMYRBO1	Follicular lymphoma	2A80	Approved	[17]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[18]
Leniolisib	DMWAD93	Stomach cancer	2B72	Approved	[19]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[5]
INCB50465	DMZJP2T	Diffuse large B-cell lymphoma	2A81	Phase 2	[20]
ME-401	DMK0UOY	Follicular lymphoma	2A80	Phase 2	[20]
RP6530	DMYILGK	Chronic lymphocytic leukaemia	2A82.0	Phase 2	[20]
Parsaclisib	DMYBIFS	Follicular lymphoma	2A80	Phase 2	[21]

Drug(s) Targeting PI3-kinase alpha (PIK3CA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[15]
Alpelisib	DMEXMYK	Breast cancer	2C60-2C65	Approved	[22]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[5]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[23]
LY3023414	DMD9KYF	Prostate cancer	2C82.0	Phase 2	[24]
MLN1117	DMCVBQD	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[25]
PWT-33597	DMJY15D	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
BLY719	DMYHNV3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]
HHCYH33	DMRQ4L6	Breast cancer	2C60-2C65	Phase 1	[27]
LY3849524	DM8I68X	Breast cancer	2C60-2C65	Phase 1	[28]

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	[29]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[18]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[5]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[20]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[30]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[20]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[31]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[32]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[32]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[33]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase alpha (PIK3CA)	TTEUNMR	PK3CA_HUMAN	Inhibitor	[3]
PI3-kinase beta (PIK3CB)	TTTHBCA	PK3CB_HUMAN	Inhibitor	[3]
PI3-kinase delta (PIK3CD)	TTGBPJE	PK3CD_HUMAN	Inhibitor	[3]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[4]

References

• [1] ClinicalTrials.gov (NCT04495621) MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01) (C-PRECISE-01). 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: 7743).
• [3] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [4] Company report (Chugai-pharm)
• [5] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [6] 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).
• [7] National Cancer Institute Drug Dictionary (drug id 751594).
• [8] 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).
• [9] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [10] 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.
• [11] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [12] 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.
• [13] 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.
• [14] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.
• [15] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [16] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [18] 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.
• [19] Effective "activated PI3K syndrome"-targeted therapy with the PI3K inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316.
• [20] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [21] Parsaclisib, a potent and highly selective PI3K inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019 Apr 18;133(16):1742-1752.
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [23] Company report (BioOncology)
• [24] Company report (Lilly)
• [25] National Cancer Institute Drug Dictionary (drug id 714372).
• [26] In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer Res. 2015 Jan;35(1):175-82.
• [27] Adaptive resistance to PI3Kalpha-selective inhibitor CYH33 is mediated by genomic and transcriptomic alterations in ESCC cells. Cell Death Dis. 2021 Jan 14;12(1):85.
• [28] ClinicalTrials.gov (NCT05307705) A Study of LOXO-783 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With Advanced Breast Cancer and Other Solid Tumors With a PIK3CA H1047R Mutation. U.S.National Institutes of Health.
• [29] 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.
• [30] 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.
• [31] 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).
• [32] 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).
• [33] 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.