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

General Information of Drug (ID: DMSHE70)

• Drug Name: GSK2141795 Drug Info
• Synonyms: Uprosertib; 1047634-65-0; GSK2141795; UNII-ZXM835LQ5E; Uprosertib (GSK2141795); GSK2141795C; ZXM835LQ5E; GSK795; GSK-2141795; 2-Furancarboxamide, N-[(1S)-2-amino-1-[(3,4-difluorophenyl)methyl]ethyl]-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-;2-Furancarboxamide, N-[(1S)-2-amino-1-[(3,4-difluorophenyl)methyl]ethyl]-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-; Uprosertib [USAN:INN]; Uprosertib (USAN/INN); Uprosertib, GSK2141795; SCHEMBL168584; GTPL7902; CHEMBL3137336; MolPort-044-560-307; AXTAPYRUEKNRBA-JTQLQIEISA-N

Indication

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 2	[1]
Lymphoma	2A80-2A86	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 51042438
  ChEBI ID: CHEMBL3137336
  CAS Number: CAS 1047634-65-0
  TTD Drug ID: DMSHE70

Molecule-Related Drug Atlas

Drug(s) Targeting RAC-gamma serine/threonine-protein kinase (AKT3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[5]
ARQ 092	DM5WK0J	Proteus syndrome	LD2C	Phase 2	[6]
MK-2206	DMT1OZ6	Rectal adenocarcinoma	2B92	Phase 2	[7]
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
LYS-6KAKT1	DMLXGAI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
LY2780301	DM93AJW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
XL418	DME0F5W	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
SR13668	DMO5760	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
TCN-P	DMV0AH8	Acute myeloid leukaemia	2A60	Phase 1	[13]
GSK690693	DMRBVHE	Haematological malignancy	2B33.Y	Phase 1	[14]

Drug(s) Affected By Tumor necrosis factor receptor superfamily member 6 (FAS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[17]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[18]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[19]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[20]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[21]
Fructose	DM43AN2	Vomiting	MD90	Approved	[22]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[23]

Drug(s) Affected By Proline-rich AKT1 substrate 1 (AKT1S1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[24]
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[28]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[29]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[30]
Cabazitaxel	DMPAZHC	Breast cancer	2C60-2C65	Approved	[31]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[32]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[33]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Post-Translational Modifications	[3]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Protein Interaction/Cellular Processes	[4]

References

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• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] DOI: 10.1016/S1359-6349(10)71767-5
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• [21] Regulatory role of KEAP1 and NRF2 in PPAR expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radic Biol Med. 2012 Aug 15;53(4):758-68. doi: 10.1016/j.freeradbiomed.2012.05.041. Epub 2012 Jun 7.
• [22] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [23] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [25] Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
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• [27] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [28] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [29] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [30] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [31] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
• [32] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [33] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.