Details of the Drug

General Information of Drug (ID: DM6JN19)

• Drug Name: ME-344
• Synonyms: NV-128; NV-344; MTOR inhibitor (cancer), Novogen; MTOR inhibitors (cancer), Marshall Edwards

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 1/2	[1]
Solid tumour/cancer	2A00-2F9Z	Preclinical	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 348.4
  Logarithm of the Partition Coefficient (xlogp); 4.4
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C22H20O4
  IUPAC Name: (3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol
  Canonical SMILES: CC1=C(C=CC2=C1OC[C@H]([C@H]2C3=CC=C(C=C3)O)C4=CC=C(C=C4)O)O
  InChI: InChI=1S/C22H20O4/c1-13-20(25)11-10-18-21(15-4-8-17(24)9-5-15)19(12-26-22(13)18)14-2-6-16(23)7-3-14/h2-11,19,21,23-25H,12H2,1H3/t19-,21-/m0/s1
  InChIKey: QVCAATSEPLQVBX-FPOVZHCZSA-N
• Cross-matching ID:
  PubChem CID: 68026984
  CAS Number: 1374524-68-1
  DrugBank ID: DB13062
  TTD ID: D03IXK
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Mammalian target of rapamycin complex 1 (mTORC1)	TTX4GLS	MTOR_HUMAN-RPTOR_HUMAN-LST8_HUMAN-AKTS1_HUMAN-DPTOR_HUMAN	Inhibitor	[1]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[3]
Target of rapamycin complex 2 MAPKAP1 (MTORC2)	TTWDKCL	SIN1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1)	OTAYZZE6	AL3A1_HUMAN	Gene/Protein Processing	[4]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[5]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Gene/Protein Processing	[4]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Gene/Protein Processing	[4]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Gene/Protein Processing	[4]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Gene/Protein Processing	[4]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Gene/Protein Processing	[4]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Gene/Protein Processing	[4]
NADH dehydrogenase 1 alpha subcomplex subunit 9, mitochondrial (NDUFA9)	OTMKQJJ8	NDUA9_HUMAN	Protein Interaction/Cellular Processes	[6]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Gene/Protein Processing	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serine/threonine-protein kinase mTOR (mTOR)	DTT	MTOR	2.16E-05	-0.44	-2.3

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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: 7961).
• [3] National Cancer Institute Drug Dictionary (drug id 728650).
• [4] Isoflavone ME-344 Disrupts Redox Homeostasis and Mitochondrial Function by Targeting Heme Oxygenase 1. Cancer Res. 2019 Aug 15;79(16):4072-4085. doi: 10.1158/0008-5472.CAN-18-3503. Epub 2019 Jun 21.
• [5] Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344. J Pharmacol Exp Ther. 2016 Aug;358(2):199-208. doi: 10.1124/jpet.115.229344. Epub 2016 Jun 2.
• [6] Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I). Am J Cancer Res. 2015 Jan 15;5(2):689-701. eCollection 2015.