MORF-627
MORF-627 is a highly selective, orally active integrin αvβ6 inhibitor. By blocking TGF-β1 activation and pSMAD2 signaling, MORF-627 significantly reduces collagen deposition, epithelial-mesenchymal transition markers, and structural changes in fibrotic cells. MORF-627 exhibits significant antifibrotic efficacy without genotoxicity in idiopathic pulmonary fibrosis models. However, MORF-627 induces bladder epithelial proliferation and early invasive urothelial carcinoma in cynomolgus monkeys and human cells, and this toxic effect can be reversed by exogenous TGF-β. MORF-627 can be used for studying the pathological mechanisms of pulmonary fibrosis and evaluating drug safety.
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- No. CAS: 2412688-16-3
- Fòrmula: C31H40FN3O4
- Peso molecular:537.67
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Almacenamiento:
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Actividad biológica
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αvβ6 1.1 nM (IC50) |
MORF-627 potently and selectively inhibits purified human integrin αvβ6 with an IC50 of 1.1 nM, exhibiting 450-fold and 300-fold selectivity over αvβ1 and αvβ8, respectively[1].
MORF-627 inhibits the binding of proTGF-β1 to HEK293 cells overexpressing human αvβ6, with an IC50 of 9.2 nM[1].
MORF-627 potently inhibits αvβ6-mediated TGF-β1 activation in a cell co-culture system, with an IC50 of 2.63 nM after 24 h of treatment[1].
MORF-627 inhibits the mRNA expression of ECM proteins in a co-culture system of primary fibroblasts and epithelial cells derived from human idiopathic pulmonary fibrosis (IPF)[1].
MORF-627 (0.01-3 μM; 3 d) induces dose-dependent proliferation of primary human bladder epithelial cells, while co-administration of 5 ng/mL exogenous TGF-β1 reverses this effect[3].
MORF-627 (0.01-3 μM; 3 d) induces dose-dependent proliferation of primary human alveolar epithelial cells within 3 days, and this effect is reversed by co-administration of 5 ng/mL exogenous TGF-β1[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:coculture of human primary epithelial cells expressing αvβ6 and human IPF fibroblasts
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Concentration:dose range
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Incubation Time:72 h
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Result:Inhibited COL1A1 mRNA expression with an IC50 of 1.8 nM.
Inhibited COL3A1 mRNA expression with an IC50 of 12.8 nM.
Inhibited FN mRNA expression with an IC50 of 20.3 nM.
| Species | Dose | Route | CL | Vss | T1/2 | AUC0-inf | Cmax | Tmax | F |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 18.0 mL/min/kg | 2.07 L/kg | 1.9 h | 0.94 μg·h/mL | / | / | / |
| Rat[1] | 1 mg/kg | i.v. | 27.6 mL/min/kg | 3.08 L/kg | 1.9 h | 0.61 μg·h/mL | / | / | / |
| Dog[1] | 1 mg/kg | i.v. | 9.53 mL/min/kg | 1.84 L/kg | 4.9 h | 2.97 μg·h/mL | / | / | / |
| Cynomolgus Monkey[1] | 1 mg/kg | i.v. | 10.5 mL/min/kg | 2.45 L/kg | 4.9 h | 1.59 μg·h/mL | / | / | / |
| Mice[1] | 30 mg/kg | p.o. | / | / | 2.6 h | 19 | 7.6 μg/mL | 0.25 h | 66 % |
| Rat[1] | 30 mg/kg | p.o. | / | / | 1.8 h | 14 | 14 μg/mL | 0.25 h | 74 % |
| Cynomolgus Monkey[1] | 5 mg/kg | p.o. | / | / | 4.8 h | 1.6 μg·h/mL | 0.54 μg/mL | 1.0 h | 16 % |
MORF-627 (1-10 mg/kg; p.o.; twice daily; for 14 consecutive days) reduces fibrosis severity and collagen deposition in a bleomycin-induced chronic mouse model of pulmonary fibrosis[1].
MORF-627 induces epithelial proliferative changes in the bladder of 33% of tested cynomolgus macaques 28 days after administration[2].
MORF-627 (administered via gavage; daily; for consecutive 28 days at 30-180-120 mg/kg/day) induces dose-related proliferation of bladder epithelial cells; 33% of treated cynomolgus monkeys develop early invasive urothelial carcinoma, and the Ki67 proliferation index of urothelial cells is significantly increased in all dose groups[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 7 weeks old, bleomycin-induced chronic model)[1]
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Dosage:1-10 mg/kg
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Administration:p.o.; twice daily; 14 days
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Result:Produced a statistically significant 33% reduction in the Modified Ashcroft Score compared to vehicle controls at 1 mg/kg, 3 mg/kg, and 10 mg/kg doses.
Significantly reduced total collagen deposition by 31%, decreased collagen fiber density, and reduced the collagen structure index compared to vehicle controls at 3 mg/kg dose.
Showed a trend toward reduced Picro Sirius Red positive area, which did not reach statistical significance.
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Animal Model:Macaca fascicularis (2-5 years of age, 2.7-4.3 kg, both sexes, mainland Asia origin)[3]
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Dosage:30 mg/kg/day; 60 mg/kg/day; 180/120 mg/kg/day (initial 3 days at 180 mg/kg/day, then 25 days at 120 mg/kg/day)
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Administration:oral gavage; daily; 28 days
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Result:Induced early-stage invasive urothelial carcinoma in 2 of 6 monkeys at 180/120 mg/kg/day.
Showed significantly increased urothelial cell proliferation, with Ki67 scores of 48 and 49 positive nuclei per 1000 urothelial cells in monkeys with tumors at 180/120 mg/kg/day, and Ki67 scores of 55 and 17 positive nuclei per 1000 urothelial cells in one male and one female monkey at 30 mg/kg/day, respectively.
Reached mean steady-state plasma Cmax levels (total) of 2.6 μM on day 28 at 30 mg/kg/day and 7.8 μM on day 28 at 120 mg/kg/day, exceeding the integrin αvβ6 cellular IC50.
Caused no treatment-related clinical signs, body weight changes, or food consumption effects at 30, 60, or 120 mg/kg/day.
Chemical Information
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No. CAS 2412688-16-3
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Peso molecular 537.67
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Fòrmula C31H40FN3O4
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SMILES
OC([C@@H](N1C[C@@H](CC1)OCCCCC(N2)=CC=C3C2=NCCC3)C4=C(C=CC(F)=C4)[C@@H]5CCC6(CO5)CC6)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
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Ficha de datos (277 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Harrison BA, et al. The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin αvβ6 Inhibitor for Fibrosis. J Med Chem. 2024;67(21):18656-18681. [Content Brief]
[2]. Golovina EL, et al. Therapeutic Prospects of αv Integrins Inhibition in Fibrotic Lung Diseases and Carcinogenesis. Int J Mol Sci. 2025;26(13):6202. Published 2025 Jun 27. [Content Brief]
[3]. Guffroy M, et al. Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques. Toxicol Sci. 2023;191(2):400-413. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MORF-627 Related Classifications
HY-149136 Related Classifications
Powered by Bioz
- MORF-627
- 2412688-16-3
- MORF627
- MORF 627
- Integrin
- TGF-beta/Smad
- early-stage invasive urothelial carcinoma
- idiopathic pulmonary fibrosis
- cynomolgus macaques
- integrin αvβ6
- epithelial-to-mesenchymal transition
- pSMAD2
- TGF-β1
- collagen deposition
- human bladder epithelial cells
- extracellular matrix
- Inhibitor
- inhibitor
- inhibit