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

General Information of Drug (ID: DMCED9U)

• Drug Name: IRX-5183 Drug Info
• Synonyms: AGN-195183; NRX-195183; NRX-5183; VTP-195183; VTP-5183; IRX-5183 (oral, autoimmune disease), Io Therapeutics; RARa (oral, cancer/autoimmune disease), Io Therapeutics; RARa agonist (topical, skin/eye diseases), Io Therapeutics; Retinoic acid receptor alpha agonist (oral, cancer/autoimmune disease), Io Therapeutics; Retinoic acid receptor alpha agonist (topical, skin/eye diseases), Io Therapeutics; IRX-5183 (oral, cancer/autoimmune disease), Io Therapeutics; IRX-5183 (topical, skin/eye diseases), Io Therapeutics

Indication

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

• Cross-matching ID:
  PubChem CID: 9867758
  CAS Number: CAS 367273-07-2
  TTD Drug ID: DMCED9U

Molecule-Related Drug Atlas

Drug(s) Targeting Retinoic acid receptor alpha (RARA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamibarotene	DM3G74J	T-cell leukaemia	2A90	Phase 3	[4]
SY-1425	DMH8UF0	Acute myeloid leukaemia	2A60	Phase 1	[1]
PMID27336223-Compound-4	DMJFSOM	N. A.	N. A.	Patented	[5]
PMID27336223-Compound-5	DM6E50A	N. A.	N. A.	Patented	[5]
LG100268	DM41RK2	Acquired immune deficiency syndrome	1C62.3	Discontinued in Phase 1	[6]
CD666	DMC8X9Y	Discovery agent	N.A.	Investigative	[7]
AGN193109	DMC0YOE	Discovery agent	N.A.	Investigative	[8]
AGN193836	DMEB93D	Discovery agent	N.A.	Investigative	[9]
BMS614	DMZWNO9	Discovery agent	N.A.	Investigative	[10]
Ro-40-0655	DM8PYAN	Colorectal cancer	2B91.Z	Investigative	[11]

Drug(s) Targeting Retinoic acid receptor RXR (RXR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IRX4204	DM9SCME	Breast cancer	2C60-2C65	Phase 1	[1]

Drug(s) Affected By Steryl-sulfatase (STS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[12]
Tazarotene	DM8SMD1	Acne vulgaris	ED80	Approved	[3]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[14]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[15]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Danazol	DML8KTN	Menorrhagia	GA20.50	Approved	[17]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[3]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Retinoic acid receptor alpha (RARA)	TTW38KT	RARA_HUMAN	Agonist	[2]
Retinoic acid receptor RXR (RXR)	TTP7WQM	NOUNIPROTAC	Agonist	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Steryl-sulfatase (STS)	OTXTJQPC	STS_HUMAN	Gene/Protein Processing	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Retinoic acid receptor alpha and retinoid X receptor specific agonists reduce renal injury in established chronic glomerulonephritis of the rat. J Mol Med (Berl). 2004 Feb;82(2):116-25.
• [3] Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways. J Cell Biochem. 2006 Feb 1;97(2):327-50. doi: 10.1002/jcb.20579.
• [4] Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-12.
• [5] Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.Expert Opin Ther Pat. 2016 Aug;26(8):957-71.
• [6] Placental steroidogenesis in rats is independent of signaling pathways induced by retinoic acids. Gen Comp Endocrinol. 2009 Sep 15;163(3):285-91.
• [7] Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977-83.
• [8] Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des. 2000 Jan;6(1):25-58.
• [9] Synthesis and biological activity of retinoic acid receptor-alpha specific amides. Bioorg Med Chem Lett. 2002 Nov 4;12(21):3145-8.
• [10] Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
• [11] Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8.
• [12] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [13] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [14] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Synthesis and steroid sulphatase inhibitory activity of C19- and C21-steroidal derivatives bearing a benzyl-inhibiting group. Eur J Med Chem. 2001 Jul-Aug;36(7-8):659-71. doi: 10.1016/s0223-5234(01)01262-4.