Details of the Drug

General Information of Drug (ID: DM4SOAW)

• Drug Name: URSOLIC ACID
• Synonyms: Ursolic acid; Prunol; Malol; Urson; 77-52-1; 3beta-Hydroxyurs-12-en-28-oic acid; (3beta)-3-Hydroxyurs-12-en-28-oic acid; 3beta-Hydroxy-12-ursen-28-ic acid; UNII-P3M2575F3F; CHEBI:9908; CCRIS 7123; EINECS 201-034-0; CHEMBL169; Merotaine; AI3-03109; NSC4060; P3M2575F3F; NSC-4060; Urs-12-en-28-oic acid, 3-hydroxy-, (3beta)-; HNMR; .beta.-Ursolic acid; NSC 4060; NSC 167406

Indication

Disease Entry	ICD 11	Status	REF
Metabolic syndrome x	5C50-5D2Z	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 456.7
  Logarithm of the Partition Coefficient (xlogp); 7.3
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C30H48O3
  IUPAC Name: (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
  Canonical SMILES: C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)O)C)C)[C@@H]2[C@H]1C)C)C(=O)O
  InChI: InChI=1S/C30H48O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h8,18-19,21-24,31H,9-17H2,1-7H3,(H,32,33)/t18-,19+,21+,22-,23+,24+,27+,28-,29-,30+/m1/s1
  InChIKey: WCGUUGGRBIKTOS-GPOJBZKASA-N
• Cross-matching ID:
  PubChem CID: 64945
  ChEBI ID: CHEBI:9908
  CAS Number: 77-52-1
  DrugBank ID: DB15588
  TTD ID: D07LUJ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	TTN7BL9	DHI1_HUMAN	Inhibitor	[2]
Glycogen phosphorylase muscle form (GP)	TTZHY6R	PYGM_HUMAN	Inhibitor	[3]
Herpes simplex virus DNA polymerase UL30 (HSV UL30)	TTIU7X1	DPOL_HHV11	Inhibitor	[4]
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Inhibitor	[5]
PTPN1 messenger RNA (PTPN1 mRNA)	TTELIN2	PTN1_HUMAN	Inhibitor	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Gene/Protein Processing	[7]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Post-Translational Modifications	[8]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[10]
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Drug Response	[11]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[12]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Gene/Protein Processing	[11]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[13]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[13]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Gene/Protein Processing	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Metabolic syndrome x
• ICD Disease Classification: 5C50-5D2Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glycogen phosphorylase muscle form (GP)	DTT	PYGM	2.69E-01	-0.23	-0.14
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	DTT	HSD11B1	2.03E-01	-0.01	-0.08
PTPN1 messenger RNA (PTPN1 mRNA)	DTT	PTPN1	9.44E-01	7.21E-03	0.08

References

• [1] ClinicalTrials.gov (NCT02337933) Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome. U.S. National Institutes of Health.
• [2] 11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational a... Bioorg Med Chem. 2010 Feb 15;18(4):1507-15.
• [3] Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase. J Nat Prod. 2009 Aug;72(8):1414-8.
• [4] DNA polymerase beta inhibitors from Baeckea gunniana. J Nat Prod. 1999 Dec;62(12):1624-6.
• [5] Synthesis of benzoyl phenyl benzoates as effective inhibitors for phospholipase A2 and hyaluronidase enzymes. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4100-4.
• [6] Cytotoxic and PTP1B inhibitory activities from Erythrina abyssinica. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6745-9.
• [7] Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines. Toxicol In Vitro. 2011 Oct;25(7):1274-80. doi: 10.1016/j.tiv.2011.04.014. Epub 2011 Apr 20.
• [8] Ursolic acid induces autophagy in U87MG cells via ROS-dependent endoplasmic reticulum stress. Chem Biol Interact. 2014 Jul 25;218:28-41. doi: 10.1016/j.cbi.2014.04.017. Epub 2014 May 5.
• [9] Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells. Oncol Rep. 2005 Aug;14(2):507-12.
• [10] Selective in vitro anti-melanoma activity of ursolic and oleanolic acids. Toxicol Mech Methods. 2018 Feb;28(2):148-156. doi: 10.1080/15376516.2017.1373881. Epub 2017 Sep 29.
• [11] Ursolic acid induces doxorubicin-resistant HepG2 cell death via the release of apoptosis-inducing factor. Cancer Lett. 2010 Dec 1;298(1):128-38. doi: 10.1016/j.canlet.2010.06.010. Epub 2010 Jul 13.
• [12] Ursolic acid reduces Adriamycin resistance of human ovarian cancer cells through promoting the HuR translocation from cytoplasm to nucleus. Environ Toxicol. 2021 Feb;36(2):267-275. doi: 10.1002/tox.23032. Epub 2020 Oct 3.
• [13] Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines. Toxicol In Vitro. 2010 Apr;24(3):842-8. doi: 10.1016/j.tiv.2009.12.008. Epub 2009 Dec 22.