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

General Information of Drug (ID: DMJY15D)

• Drug Name: PWT-33597 Drug Info
• Synonyms: PI3 kinase alpha/mTOR dual inhibitor (cancer), Pathway Therapeutics

Indication

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

• Cross-matching ID:
  PubChem CID: 46917355
  CAS Number: CAS 1246203-32-6
  TTD Drug ID: DMJY15D

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	[4]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[5]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[6]
Everolimus	DM8X2EH	Advanced cancer	2A00-2F9Z	Approved	[7]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[8]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[9]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[10]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[12]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[8]

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	[13]
Alpelisib	DMEXMYK	Breast cancer	2C60-2C65	Approved	[14]
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[15]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[16]
LY3023414	DMD9KYF	Prostate cancer	2C82.0	Phase 2	[17]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[18]
MLN1117	DMCVBQD	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[19]
BLY719	DMYHNV3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[20]
HHCYH33	DMRQ4L6	Breast cancer	2C60-2C65	Phase 1	[21]
LY3849524	DM8I68X	Breast cancer	2C60-2C65	Phase 1	[22]

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	Modulator	[2]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Modulator	[3]

References

• [1] ClinicalTrials.gov (NCT01407380) Study of PWT33597 Mesylate in Subjects With Advanced Malignancies. U.S. National Institutes of Health.
• [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] PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early phase clinical trials
• [4] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [5] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 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.
• [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. (Target id: 2109).
• [9] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [10] 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.
• [11] 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.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [15] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [16] Company report (BioOncology)
• [17] Company report (Lilly)
• [18] The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81.
• [19] National Cancer Institute Drug Dictionary (drug id 714372).
• [20] In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer Res. 2015 Jan;35(1):175-82.
• [21] 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.
• [22] 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.