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

General Information of Drug (ID: DM4OQRD)

• Drug Name: HIF-1alpha Drug Info
• Synonyms: Unii-NA856793UT; 192705-79-6; PD-166866; PD166866; PD 166866; UNII-NA856793UT; CHEMBL299763; NA856793UT; 1-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butylurea; 1-(2-Amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl)-3-tert-butyl urea; Urea,N-[2-amino-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)-; 1-[2-Amino-6-(3,5-dimethoxyphenyl)-pyrido[2,3-d]pyrimidin-7-yl]-3-tert-butyl urea; 6-arylpyrido[2,3-d]pyrimidine deriv 25; AC1NS3U5; SCHEMBL1248489; BDBM3443; CTK4E1060

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 4	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 5328127
  ChEBI ID: CHEBI:156259
  CAS Number: CAS 192705-79-6
  TTD Drug ID: DM4OQRD

Molecule-Related Drug Atlas

Drug(s) Targeting Fibroblast growth factor receptor (FGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Erdafitinib	DMI782S	Bladder cancer	2C94	Approved	[5]
Futibatinib	DMWM4D0	Intrahepatic cholangiocarcinoma	2C12.10	Approved	[6]
Infigratinib	DMNKBEC	Cholangiocarcinoma	2C12.10	Approved	[7]
ARQ-087	DM02BVQ	Intrahepatic cholangiocarcinoma	2C12.10	Phase 3	[7]
AZD4547	DM3827C	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[7]
Debio 1347	DMZW50O	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
BAY1163877	DMCSGJ2	Bladder cancer	2C94	Phase 2	[9]
ICP-192	DM524GR	Bladder cancer	2C94	Phase 2	[10]
PRN1371	DMR7BAO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
PD173074	DMP0N4U	Nasopharyngeal carcinoma	2B6B	Investigative	[2]

Drug(s) Targeting Hypoxia-inducible factor 1 alpha (HIF-1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IT-101	DMNDGWE	Solid tumour/cancer	2A00-2F9Z	Phase 3	[11]
2-Methoxyestradiol	DMGBPME	Pulmonary arterial hypertension	BB01.0	Phase 2	[12]
PX-478	DM4AU8K	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
EZN-2968	DM2NBC7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
ENMD-1198	DM9BJ3G	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
Pyrrolidine carboxamide derivative 1	DMJK98Z	N. A.	N. A.	Patented	[16]

Drug(s) Affected By Fibroblast growth factor receptor 1 (FGFR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[17]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[18]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[19]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[20]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Lenalidomide	DM6Q7U4	Adult T-cell leukemia/lymphoma		Approved	[22]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[22]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor (FGFR)	TT0LF7H	NOUNIPROTAC	Antagonist	[2]
Hypoxia-inducible factor 1 alpha (HIF-1A)	TTQHWNA	HIF1A_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Fibroblast growth factor receptor 1 (FGFR1)	OT4GLCXW	FGFR1_HUMAN	Gene/Protein Processing	[4]

References

• [1] ClinicalTrials.gov (NCT00880672) Effect of Dutasteride on HIF-1alpha and VEGF in the Prostate. U.S. National Institutes of Health.
• [2] Tumor angiogenesis as a therapeutic target. Drug Discov Today. 2001 Oct 1;6(19):1005-1024.
• [3] A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther. 2008 Nov;7(11):3598-608.
• [4] Essential role of fibroblast growth factor signaling in preadipoctye differentiation. J Clin Endocrinol Metab. 2005 Feb;90(2):1226-32. doi: 10.1210/jc.2004-1309. Epub 2004 Nov 2.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [6] TAS-120, a highly potent and selective irreversible FGFR inhibitor, is effective in tumors harboring various FGFR gene abnormalities. Molecular Cancer Therapeutics. 01/2014; 12(11_Supplement):A270-A270.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther. 2014 Nov;13(11):2547-58.
• [9] Preclinical profile of BAY 1163877 - a selective pan-FGFR inhibitor in phase 1 clinical trial. Cancer Research. 10/2014; 74(19 Supplement):1739-1739.
• [10] Clinical pipeline report, company report or official report of InnoCare Pharma.
• [11] CRLX101, an investigational camptothecin-containing nanoparticle-drug conjugate, targets cancer stem cells and impedes resistance to antiangiogenic therapy in mouse models of breast cancer. Breast Cancer Res Treat. 2015 Apr;150(3):559-67.
• [12] 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squam... Clin Cancer Res. 2004 Dec 15;10(24):8665-73.
• [13] The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol Cancer Ther. 2009 Apr;8(4):947-58.
• [14] Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1), in patients with refractory solid tumors.Cancer Chemother Pharmacol.2014 Feb;73(2):343-8.
• [15] ENMD-1198, a new analogue of 2-methoxyestradiol, displays both antiangiogenic and vascular-disrupting properties. Mol Cancer Ther. 2010 May;9(5):1408-18.
• [16] Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015).Expert Opin Ther Pat. 2016;26(3):309-22.
• [17] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [18] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [19] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [20] Effects of chlorpromazine with and without UV irradiation on gene expression of HepG2 cells. Mutat Res. 2005 Aug 4;575(1-2):47-60. doi: 10.1016/j.mrfmmm.2005.03.002. Epub 2005 Apr 26.
• [21] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [22] Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
• [23] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [24] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [25] 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.