Details of the Drug

General Information of Drug (ID: DMWQIJX)

• Drug Name: Celastrol
• Synonyms: Tripterin; Tripterine; Celastrol, Celastrus scandens; (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid; (2R,4aS,6aS,12bR,14aS,14bR)-10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylic acid; 3-Hydroxy-24-nor-2-oxo-1(10),3,5,7-friedelatetraen-29-oic Acid

Indication

Disease Entry	ICD 11	Status	REF
Motor neurone disease	8B60	Preclinical	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 450.6
  Logarithm of the Partition Coefficient (xlogp); 5.9
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C29H38O4
  IUPAC Name: (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid
  Canonical SMILES: CC1=C(C(=O)C=C2C1=CC=C3[C@]2(CC[C@@]4([C@@]3(CC[C@@]5([C@H]4C[C@](CC5)(C)C(=O)O)C)C)C)C)O
  InChI: InChI=1S/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1
  InChIKey: KQJSQWZMSAGSHN-JJWQIEBTSA-N
• Cross-matching ID:
  PubChem CID: 122724
  ChEBI ID: CHEBI:63959
  CAS Number: 34157-83-0
  TTD ID: D0I9XH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Interleukin-1 beta (IL1B)	TTRYK0X	IL1B_HUMAN	Suppressor	[1]
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Suppressor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1)	OTC7AFHT	AHSA1_HUMAN	Gene/Protein Processing	[2]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Gene/Protein Processing	[2]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Gene/Protein Processing	[2]
Alpha-crystallin B chain (CRYAB)	OTY4JGYU	CRYAB_HUMAN	Gene/Protein Processing	[3]
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Gene/Protein Processing	[2]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Gene/Protein Processing	[2]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[4]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[5]
AT-rich interactive domain-containing protein 5B (ARID5B)	OTUQ4CQY	ARI5B_HUMAN	Gene/Protein Processing	[2]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Motor neurone disease
• ICD Disease Classification: 8B60

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Interleukin-1 beta (IL1B)	DTT	IL1B	4.74E-01	8.78E-03	0.02

References

• [1] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.
• [2] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [3] The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells. J Biol Chem. 2015 Jan 16;290(3):1623-38.
• [4] Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells. Oncotarget. 2016 Jul 19;7(29):46557-46572.
• [5] Celastrol induces apoptosis in non-small-cell lung cancer A549 cells through activation of mitochondria- and Fas/FasL-mediated pathways. Toxicol In Vitro. 2011 Aug;25(5):1027-32. doi: 10.1016/j.tiv.2011.03.023. Epub 2011 Apr 3.