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

General Information of Drug (ID: DM4RK6P)

• Drug Name: AR-12 Drug Info
• Synonyms: 2-Amino-N-(4-(5-(phenanthren-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide; OSU-03012; 742112-33-0; OSU 03012; OSU03012; PDK1 inhibitor AR-12; OSU-03012 (AR-12); UNII-EX3O2Q61UV; 2-amino-N-(4-(5-(phenanthren-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide; AR 12; EX3O2Q61UV; CHEMBL1650595; 2-amino-N-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]acetamide; 2-Amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]acetamide; PubChem22592; MLS006010170; SCHEMBL570472; GTPL8005; C26H19F3N4O; EX-A253; DTXSID50225206; CHEBI:131196; MolPort-009-019-120

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 10027278
  ChEBI ID: CHEBI:131196
  CAS Number: CAS 742112-33-0
  TTD Drug ID: DM4RK6P

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphoinositide dependent protein kinase-1 (PDPK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[4]
PMID20005102C1	DMMESBW	Discovery agent	N.A.	Investigative	[5]
BX-912	DMZA45C	Discovery agent	N.A.	Investigative	[6]
BX-795	DMRIMLJ	Discovery agent	N.A.	Investigative	[6]
PHT-427	DMI96Y3	Discovery agent	N.A.	Investigative	[7]
PF-5177624	DMUOFT0	Solid tumour/cancer	2A00-2F9Z	Investigative	[8]
GSK-2334470	DM3BI7R	Solid tumour/cancer	2A00-2F9Z	Investigative	[9]

Drug(s) Affected By RAC-alpha serine/threonine-protein kinase (AKT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Capivasertib	DM9SKW8	Breast cancer	2C60-2C65	Approved	[10]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[11]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[12]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[13]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Imiquimod	DM1TMA3	Alopecia areata	ED70.2	Approved	[16]
Selenium	DM25CGV	N. A.	N. A.	Approved	[17]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[18]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[19]

Drug(s) Affected By 3-phosphoinositide-dependent protein kinase 1 (PDPK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[23]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[24]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[25]
Amiloride	DMRTSGP	Congestive heart failure	BD10	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[24]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphoinositide dependent protein kinase-1 (PDPK1)	TT9QBI6	PDPK1_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
3-phosphoinositide-dependent protein kinase 1 (PDPK1)	OTT09ZVP	PDPK1_HUMAN	Drug Response	[3]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Drug Response	[3]

References

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• [5] 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):679-83.
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• [7] Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17.
• [8] Targeting 3-phosphoinoside-dependent kinase-1 to inhibit insulin-like growth factor-I induced AKT and p70 S6 kinase activation in breast cancer cells. PLoS One. 2012;7(10):e48402.
• [9] Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf(V600E)::Pten(-/-) melanoma. Oncogene. 2014 Aug 21;33(34):4330-9.
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• [11] Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent. Mol Cancer. 2010 Aug 20;9:220.
• [12] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [13] -Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-B Signaling Pathway. J Biochem Mol Toxicol. 2016 Mar;30(3):148-57. doi: 10.1002/jbt.21773. Epub 2016 Jan 6.
• [14] Dihydromyricetin suppresses tumor growth via downregulation of the EGFR/Akt/survivin signaling pathway. J Biochem Mol Toxicol. 2023 Jun;37(6):e23328. doi: 10.1002/jbt.23328. Epub 2023 Feb 19.
• [15] Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009 Aug;110(2):376-88. doi: 10.1093/toxsci/kfp101. Epub 2009 May 18.
• [16] Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2015 Mar;35(3):1063-76. doi: 10.1111/liv.12626. Epub 2014 Jul 30.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [19] Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
• [20] Arsenic trioxide inhibits translation of mRNA of bcr-abl, resulting in attenuation of Bcr-Abl levels and apoptosis of human leukemia cells. Cancer Res. 2003 Nov 15;63(22):7950-8.
• [21] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [22] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [23] 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.
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• [28] Differential roles of phosphoinositide-dependent protein kinase-1 and akt1 expression and phosphorylation in breast cancer cell resistance to Paclitaxel, Doxorubicin, and gemcitabine. Mol Pharmacol. 2006 Sep;70(3):1045-52. doi: 10.1124/mol.106.023333. Epub 2006 Jun 16.