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

General Information of DTT (ID: TTHBTOP)

• DTT Name: PI3-kinase gamma (PIK3CG) DTT Info
• Gene Name: PIK3CG

Molecule-Related Drug & Molecule List

2 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY 80-6946	DMLOS5R	Follicular lymphoma	2A80	Approved	[1]
IPI-145	DMWA24P	Follicular lymphoma	2A80	Approved	[2]

35 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buparlisib	DM1WEHC	Breast cancer	2C60-2C65	Phase 3	[3]
Enzastaurin	DM5H0R9	Diffuse large B-cell lymphoma	2A81	Phase 3	[4]
GDC-0032	DMT4QHD	Breast cancer	2C60-2C65	Phase 3	[4]
Rigosertib	DMOSTXF	Myelodysplastic syndrome	2A37	Phase 3	[5]
AZD8154	DMK13L1	Asthma	CA23	Phase 2	[6]
BEZ235	DMKBRDL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[7]
CLR-1404	DMAW4EL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
GDC-0077	DMY6WUV	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
GDC-0084	DMA9SEY	Glioblastoma of brain	2A00.00	Phase 2	[9]
GDC-0980/RG7422	DMF3MV1	Non-hodgkin lymphoma	2B33.5	Phase 2	[10]
GDC0941	DM1YAK6	Breast cancer	2C60-2C65	Phase 2	[3]
IPI-549	DMG5Q7F	Bladder cancer	2C94	Phase 2	[4]
PF-04691502	DMS610L	Endometrial cancer	2C76	Phase 2	[11]
PF-05212384	DMBL3VD	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[8]
PX-866	DMYISJK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
SAR245409	DMQM7IL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
SF1126	DML10K3	Head and neck cancer	2D42	Phase 2	[14]
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
BGT226	DMXKDUL	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[15]
CLR-1401	DM2FSM5	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
CLR457	DM64FY7	Advanced solid tumour	2A00-2F9Z	Phase 1/2	[16]
CUDC-907	DMHIQDC	Acute myelogenous leukaemia	2A41	Phase 1/2	[17]
PA-799	DMLSYJQ	Colorectal cancer	2B91.Z	Phase 1/2	[18]
TG100-115	DMON4IL	Angioedema	4A00.15	Phase 1/2	[19]
ZX-101A	DM65AV2	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[20]
AZD8186	DMWYF1H	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
DS-7423	DMCFJM3	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]
GSK2126458	DMM7ZXR	Lymphoma	2A80-2A86	Phase 1	[22]
KA2237	DMFKEVO	B-cell lymphoma	2A86	Phase 1	[4]
LY294002	DMY1AFS	Neuroblastoma	2D11.2	Phase 1	[23]
P-7170	DMIYQEM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
Perifosine	DMVYRH2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[24]
VS-5584	DMMO3G5	Malignant mesothelioma	2C26.0	Phase 1	[25]
ZSTK474	DMVIMQX	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]

5 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adyvia	DMZ7WKN	Type-2 diabetes	5A11	Discontinued in Phase 2	[27]
GSK1059615	DMI6KQM	Breast cancer	2C60-2C65	Discontinued in Phase 1	[3]
PX-867	DMCNE2G	Cardiovascular disease	BA00-BE2Z	Terminated	[28]
SCR-44001	DMFZNUA	Solid tumour/cancer	2A00-2F9Z	Terminated	[29]
Wortmannin	DM8EVK5	Haematological malignancy	2B33.Y	Terminated	[30]

27 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)phenol	DM54MDH	Discovery agent	N.A.	Investigative	[31]
5-QUINOXALIN-6-YLMETHYLENE-THIAZOLIDINE-2,4-DIONE	DMVX063	Discovery agent	N.A.	Investigative	[32]
AEZS-126	DMM52FD	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
AS-604850	DM9IUSM	Discovery agent	N.A.	Investigative	[33]
BAG956	DMWC34B	Haematological malignancy	2B33.Y	Investigative	[34]
CU-906	DMY1WEM	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
CZC 24832	DMLBYFG	Discovery agent	N.A.	Investigative	[35]
CZC-19091	DMYBL5G	Inflammation	1A00-CA43.1	Investigative	[13]
Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate	DM3FH02	Discovery agent	N.A.	Investigative	[36]
Her2- and PSA-targeted TGX-D1	DM0VC84	Prostate cancer	2C82.0	Investigative	[37]
HM-5016699	DMKHVUE	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
HS-173	DM0A2UF	Discovery agent	N.A.	Investigative	[38]
KU-0060648	DMQWS6U	Discovery agent	N.A.	Investigative	[39]
LOR-220	DM71BIC	Bacterial infection	1A00-1C4Z	Investigative	[8]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[36]
Multiform PI3K inhibitors	DMW2Z4I	Inflammation	1A00-CA43.1	Investigative	[8]
Myricetin	DMTV4L0	Discovery agent	N.A.	Investigative	[40]
P-6915	DMJDI7O	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PF-03772304	DMJ0936	Solid tumour/cancer	2A00-2F9Z	Investigative	[41]
PF-4989216	DMSG6F1	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
PI-103	DMEK4TJ	Haematological malignancy	2B33.Y	Investigative	[34]
PI-3065	DMCQUWI	Discovery agent	N.A.	Investigative	[42]
PIK-75	DM9BQTX	Discovery agent	N.A.	Investigative	[31]
PKI-402	DM6NX4H	Solid tumour/cancer	2A00-2F9Z	Investigative	[43]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[44]
TGX-221	DMM0LRE	Discovery agent	N.A.	Investigative	[45]
WX-037	DM6J7OQ	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]

References

• [1] 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.
• [2] 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.
• [3] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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.
• [6] Discovery of AZD8154, a Dual PI3Kgamma-delta Inhibitor for the Treatment of Asthma. J Med Chem. 2021 Jun 24;64(12):8053-8075.
• [7] The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses. Neoplasia. 2012 Jan;14(1):34-43.
• [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: 2155).
• [9] Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol. 2012 July; 14(7): 819-829.
• [10] GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36.
• [11] PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity.Mol Cancer Ther.2011 Nov;10(11):2189-99.
• [12] 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.
• [13] 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).
• [14] 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.
• [15] Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma. Anticancer Drugs. 2012 Jan;23(1):131-8.
• [16] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [17] Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling.Clin Cancer Res.2012 Aug 1;18(15):4104-13.
• [18] Company report (Chugai-pharm)
• [19] Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic can... J Pharmacol Exp Ther. 2009 Mar;328(3):758-65.
• [20] Clinical pipeline report, company report or official report of Zenshine Pharmaceuticals
• [21] Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423. PLoS One. 2014 Feb 4;9(2):e87220.
• [22] Company report (GSK)
• [23] Clinical pipeline report, company report or official report of Genentech (2009).
• [24] Company report (Aezsinc)
• [25] VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther. 2013 Feb;12(2):151-61.
• [26] Combination of the PI3K inhibitor ZSTK474 with a PSMA-targeted immunotoxin accelerates apoptosis and regression of prostate cancer. Neoplasia. 2013 Oct;15(10):1172-83.
• [27] Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat.Am J Physiol Endocrinol Metab.2004 Sep;287(3):E463-71.
• [28] Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell death. J Pharmacol Exp Ther. 2013 Dec;347(3):669-80.
• [29] Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. PLoS One. 2010 Sep 24;5(9):e12965.
• [30] Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation. Cancer Res. 2002 Aug 15;62(16):4671-7.
• [31] 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.
• [32] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [33] Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005 Sep;11(9):936-43.
• [34] The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
• [35] A selective inhibitor reveals PI3Kgamma dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012 Apr 29;8(6):576-82.
• [36] LY294002-geldanamycin heterodimers as selective inhibitors of the PI3K and PI3K-related family. Bioorg Med Chem Lett. 2001 Apr 9;11(7):909-13.
• [37] Development of a peptide-drug conjugate for prostate cancer therapy. Mol Pharm. 2011 Jun 6;8(3):901-12.
• [38] Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis. J Med Chem. 2011 Apr 14;54(7):2455-66.
• [39] 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.
• [40] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [41] Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design. ACS Med Chem Lett. 2012 Nov 7;4(1):91-7.
• [42] Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;510(7505):407-11.
• [43] Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: di... J Med Chem. 2010 Jan 28;53(2):798-810.
• [44] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [45] PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005 May;11(5):507-14.