Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C29H22Cl3NO4 |
| Molecular Weight | 554.848 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)C1=CC=C(C=C1)[C@H]2C[C@@H]2C3=CC=C(OCC4=C(ON=C4C5=C(Cl)C=CC=C5Cl)C6CC6)C=C3Cl
InChI
InChIKey=XBUXXJUEBFDQHD-NHCUHLMSSA-N
InChI=1S/C29H22Cl3NO4/c30-23-2-1-3-24(31)26(23)27-22(28(37-33-27)16-6-7-16)14-36-18-10-11-19(25(32)12-18)21-13-20(21)15-4-8-17(9-5-15)29(34)35/h1-5,8-12,16,20-21H,6-7,13-14H2,(H,34,35)/t20-,21-/m1/s1
| Molecular Formula | C29H22Cl3NO4 |
| Molecular Weight | 554.848 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
PX-102 is a methoxyphenylcyclopropane derivative patented by Phenex Pharmaceuticals AG as Farnesoid X receptor agonists useful in the treatment and prophylaxis of FXR-mediated diseases. The Farnesoid X Receptor (FXR) is a bile acid receptor which when activated by Px-102 has a profound positive impact on cholesterol, triglyceride and glucose metabolism in liver and intestine. In preclinical studies, Px-102 potently reduces intestinal uptake of neutral lipids and cholesterol and at the same time enhances the excretion of these lipid species. In addition, Px-102 improves hepatic insulin sensitivity and shows massive hepatoprotective effects in animal models of liver cirrhosis or fibrosis. Phenex Pharmaceuticals completes a phase I trial in Healthy volunteers in Germany in 2012 and no further development report has been published.
Approval Year
| Substance Class |
Chemical
Created
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admin
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Edited
Sat Dec 16 11:43:26 UTC 2023
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Sat Dec 16 11:43:26 UTC 2023
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| Record UNII |
6TU6SUZ3BY
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| Record Status |
Validated (UNII)
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1268244-85-4
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CHEMBL3545113
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PX-20606
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admin on Sat Dec 16 11:43:26 UTC 2023 , Edited by admin on Sat Dec 16 11:43:26 UTC 2023
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PRIMARY | MedKoo CAT NO: 522554, CAS NO: 1268245-19-7(free acid)Description: PX20606, also known as PX-102, is a FXR agonist. PX20606 induces high-density lipoprotein-mediated transhepatic cholesterol efflux in mice and monkeys and prevent atherosclerosis in cholesteryl ester transfer protein transgenic low-density lipoprotein receptor (-/-) mice. PX20606 demonstrated potent plasma cholesterol-lowering activity that affected all lipoprotein species. (last updated: 3/21/2016). | ||
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1268245-19-7
Created by
admin on Sat Dec 16 11:43:26 UTC 2023 , Edited by admin on Sat Dec 16 11:43:26 UTC 2023
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6TU6SUZ3BY
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118374999
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TARGET -> AGONIST |
| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Originator: Phenex Pharmaceuticals; Class: Antihyperlipidaemic, Hepatoprotectant, Small molecule; Mechanism of Action: Farnesoid X-activated receptor agonist; New Molecular Entity: Yes; Highest Development Phase: Discontinued for Non-alcoholic fatty liver disease
Most Recent Events: 07 Feb 2015 Phenex terminates a phase II trial in Non-alcoholic fatty liver disease in Austria (PO) (EudraCT2013-002984-24), 07 Oct 2013 Phase-II clinical trials in Non-alcoholic fatty liver disease in Austria (PO)
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ACTIVE MOIETY |
Results: CCl4 rats presented with marked cirrhosis, elevated transaminases and portal hypertension. In CCl4 rats, PX treatment significantly ameliorated fibrosis (SRA: 6.99 +/- 3.15 vs. 3.97 +/- 1.64%
p < 0.001 HP: 415 +/- 86 vs. 134 +/- 14 undefined g/g
p = 0.002) and reduced Col1 (12.28 +/- 1.78 vs. 4.93 +/- 0.28
p < 0.05) and .ALPHA.SMA (7.78 +/- 1.41 vs. 2.08 +/- 0.49
p < 0.05) expression. Accordingly AST (555 +/- 30 vs. 227 +/- 83 IU/ml
p < 0.001) and ALT (538 +/- 233 vs. 193 +/- 86 IU/ml
p = 0.008) significantly decreased under PX treatment, while plasma cholesterol and triglycerides levels remained unaffected. PX treatment significantly decreased PP (11.9 +/- 1.4 vs. 9.7 +/- 1.4 mmHg
p = 0.037) and increased SMABF (8.88 +/- 2.62 vs. 13.81 +/- 2.81 ml/min/100 g
p = 0.021), while not affecting MAP (125 +/- 14 vs. 116 +/- 25 mmHg) nor HR (330 +/- 29 vs. 333 +/- 52bpm). Livers of CCl4-PX rats significantly overexpressed FXR target genes including bile salt export pump (2.5 x), small heterodimer partner (2.3 x), cystathionase (2.1 x) and dimethylargininase (1.7 x). Gene expression of endothelin-1 (0.45), PDGF-R.BETA. (0.51 x) and .ALPHA.SMA (0.61 x) was significantly reduced.
Conclusions: PX20606 treatment effectively reduces hepatic inflammation, fibrogenesis and portal pressure in cirrhotic rats.
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ACTIVE MOIETY |
Originator: Phenex Pharmaceuticals; Class: Small molecule; Mechanism of Action: Farnesoid X-activated receptor agonist; New Molecular Entity: Yes; Highest Development Phases: Discontinued for Metabolic syndrome, Non-alcoholic steatohepatitis; Most Recent Events: 01 Oct 2012 Phenex Pharmaceuticals completes a phase I trial in Healthy volunteers in Germany (NCT01998672), 01 Feb 2012 Phenex Pharmaceuticals initiates enrolment in a phase I trial for Healthy volunteers in Germany (NCT01998672), 01 Dec 2011 Phenex Pharmaceuticals completes a phase I trial in Healthy volunteers in Germany (NCT01998659)
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ACTIVE MOIETY |
Official Title: A Double-blind, Randomised, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Pharmacokinetics of Increasing Multiple Oral Doses of Px-102 to Healthy Subjects
Purpose: The purpose of this study is to assess the safety and tolerability of the FXR agonist Px-102 in healthy subjects after 7 days multiple oral dosing.
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