 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C27H36N6O3 |
| Molecular Weight | 492.61 |
| Exact Mass | 492.28 |
| Elemental Analysis | C, 65.83; H, 7.37; N, 17.06; O, 9.74 |
| CAS # | 2376257-44-0 |
| Related CAS # | 2376264-69-4 (R-isomer);2376257-44-0;2775365-40-5 (HCl);2775365-33-6 (fumarate); 2775365-31-4 (phosphate); |
| PubChem CID | 135390719 |
| Appearance | White to off-white solid powder |
| LogP | 1.8 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 14 |
| Heavy Atom Count | 36 |
| Complexity | 655 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | COCCN(CCCCC1=NC2=C(CCCN2)C=C1)CC[C@@H](C(=O)O)NC3=NC=NC4=CC=CC=C43 |
| InChi Key | CWOFQJBATWQSHL-DEOSSOPVSA-N |
| InChi Code | InChI=1S/C27H36N6O3/c1-36-18-17-33(15-5-4-8-21-12-11-20-7-6-14-28-25(20)31-21)16-13-24(27(34)35)32-26-22-9-2-3-10-23(22)29-19-30-26/h2-3,9-12,19,24H,4-8,13-18H2,1H3,(H,28,31)(H,34,35)(H,29,30,32)/t24-/m0/s1 |
| Chemical Name | (S)-4-((2-methoxyethyl)(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)amino)-2-(quinazolin-4-ylamino)butanoic acid |
| Synonyms | PLN-74809; PLN 74809; PLN74809; Bexotegrast; Bexotegrast free base, |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | αvβ6 |
| ln Vitro | In precision sectioned lung sections (PCLS), bexotegrast (PLN-74809; 1.82 µM; intestinal 7 days) significantly decreased collagen type I alpha I (COL1A1) mRNA expression by 54%. There is less Smad2 phosphorylation in bexotegrast. In PCLS produced from fibrotic lungs, bexotegrast (1.82 µM; workstation 3 days) self-regulates up to a 71% reduction in Col1a1 mRNA expression [2]. αvβ6 integrin is totally blocked by bexotegrast. Approximately 50%[2]. LAP is labeled by normal human epithelial cells with an IC50 of 39.3 nM[2]. |
| ln Vivo | Bexotegrast (PLN-74809; sidewall; 100, 250, 500 mg/kg; twice daily; from day 7 to day 21) was provided at levels necessary to inhibit bleomycin-challenged cartilage interstitial fibrillar collagen deposition. Bexotegrast dosage |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice [2] Doses: 100, 250, 500 mg/kg Route of Administration: Oral; strongly bursts Smad3 phosphorylation [2]. twice (two times) daily; from day 7 to day 21 Experimental Results: There was a dose-dependent significant reduction in interstitial fibrillar collagen deposition in mice challenged with bleomycin (3 units/kg). Dose-dependent blockade of Smad3 phosphorylation. |
| References |
[1]. De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8. Nat Commun. 2023 Sep 13;14(1):5660. [2]. Dual inhibition of αvβ6 and αvβ1 reduces fibrogenesis in lung tissue explants from patients with IPF. Respir Res. 2021 Oct 19;22(1):265. |
| Additional Infomation |
PLN-74809 is a small-molecule that dually inhibits both αvβ6 and αvβ1 to treat both idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC). The compound was granted orphan drug designation by the US FDA in August 2018 for treatment of IPF, and Pliant Therapeutics recently raised $100 million in Series C financing to support further clinical development of this compound. Phase 2a studies are currently evaluating PLN-74809 safety and efficacy for participants with IPF (NCT04396756)across 10 participating countries, and for participants with PSC (NCT04480840). In addition, the compound is also currently in Phase 2a trials (NCT04565249) for the treatment of COVID-19 related acute respiratory distress syndrome. Drug Indication Through dual inhibition of integrins αvβ6 and αvβ1, PLN-74809 reduces subsequent activation of TGF-β1, which is actively involved in the growth of fibrotic tissue in lung and bile ducts. Further studies showed that PLN-74809 inhibited collagen gene expression in PSC and IPF patient tissue. |
Solubility Data
| Solubility (In Vitro) | DMSO : 250 mg/mL (507.50 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0300 mL | 10.1500 mL | 20.3000 mL | |
| 5 mM | 0.4060 mL | 2.0300 mL | 4.0600 mL | |
| 10 mM | 0.2030 mL | 1.0150 mL | 2.0300 mL |