CD2019
CD2019 is a selective retinoic acid receptor β (RARβ) agonist, with a Kd value of 26 nM for RARβ and an AC50 value of 3.8 nM for human RARβ. CD2019 regulates downstream biological effects via the PI3K signaling pathway. CD2019 suppresses squamous metaplasia, inhibits squamous differentiation markers, maintains pseudostratified epithelial structure, induces neurite and axon growth, and promotes functional recovery; it exhibits cytotoxicity at higher concentrations and reduces endogenous retinol levels. CD2019 can be used in studies related to squamous metaplasia, spinal cord injury and embryonic malformations.
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- CAS. Nr.: 143984-56-9
- Formel: C25H26O3
- Molecular Weight:374.47
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
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RARβ 26 nM (Kd) |
CD2019 binds selectively to RARβ with a Kd value of 26.0 nM, and exhibits significantly lower affinity for the RARα and RARγ subtypes[1].
CD2019 (0.05-0.5 µM; 7 days) inhibits squamous differentiation of primary rabbit tracheal epithelial cells in a dose-dependent manner, completely abolishes the expression of CK13/CK4 at a concentration of 0.5 µM, and reduces the expression of other differentiation- and proliferation-related cytokeratins[1].
CD2019 (0.5 µM; 4 days) potently inhibits the expression of transglutaminase I, a marker of terminal squamous differentiation, in primary rabbit tracheal epithelial cells[1].
CD2019 (1.6 µM; 24 h) maintains a non-squamous, pseudostratified morphology in primary rabbit tracheal epithelial cells without inducing cell death[1].
CD2019 (0.01-1 μM; 21 h) reverses MAG-induced axon growth inhibition in cerebellar neurons of postnatal day 3 rat pups in a dose-dependent manner by activating the PI3K/Akt signaling pathway, and increases the phosphorylated Akt level by 4-fold at the concentration of 1 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:primary rabbit tracheal epithelial (RbTE) cells
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Concentration:50, 160, 500 nM
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Incubation Time:7 days
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Result:Inhibited squamous metaplasia in a dose-dependent manner.
Totally abolished the expression of CK13/CK4, cytokeratins specific to squamous metaplasia at 0.5 µM.
Diminished the expression of CK10 (a keratinizing epithelium cytokeratin) and CK14 (a basal cell cytokeratin).
Strongly reduced the expression of CK5 (a basal cell cytokeratin) and CK6 (a cell proliferation marker).
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Cell Line:primary rabbit tracheal epithelial (RbTE) cells
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Concentration:0.5 µM
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Incubation Time:4 days
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Result:Reduced transglutaminase I (TGI) expression to a negligible level; TGI is a key enzyme involved in cornified envelope formation, a marker of terminal squamous differentiation.
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Cell Line:primary rabbit tracheal epithelial (RbTE) cells
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Concentration:1.6 µM
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Incubation Time:24 h
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Result:Did not promote the formation of a sub-G1 population, indicating no induction of apoptotic cell death.
| Species | Dose | Route | T1/2 | Cmax | Tmax | CL/F | Vd/F |
|---|---|---|---|---|---|---|---|
| Mice[4] | 15 mg/kg | p.o. | 5.4 h | 2852 nM | 1.25 h | 2.7 L/h/kg | 20.8 L/kg |
CD2019 (5-15 mg/kg; p.o.; single administration) exhibits teratogenic activity in pregnant NMRI mice, inducing dose- and gestational time-dependent embryo resorption as well as a range of fetal malformations (including urinary tract defects, craniofacial abnormalities, limb defects, and sternal skeletal defects)[3].
CD2019 (15 mg/kg; p.o.; single administration) reduces plasma and embryonic retinol levels in NMRI pregnant mice on gestational day 11, and its low placental transfer rate correlates with its weak teratogenic potency[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Adult male rats[2]
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Dosage:180 ng/kg/day
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Administration:i.c.v.; daily; 14 days
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Result:Induced a 6-fold increase in cortical RARβ protein levels compared to non-lesioned vehicle-treated animals in lesioned rats.
Triggered an 8-fold increase in cortical phospho-Akt levels compared to lesioned vehicle-treated rats, with phospho-Akt co-localized in injured corticospinal tract neurons.
Promoted axonal outgrowth of BDA-labelled corticospinal tract axons around and caudal to the lesion site; at 2800 μm caudal to the lesion forelimb innervation level, there was a significant peak in BDA-positive axons compared to vehicle-treated rats.
Did not alter lesion volume or axonal sparing compared to vehicle-treated rats.
Enabled functional forelimb recovery: lesioned rats showed no significant difference in footslips compared to non-lesioned vehicle-treated rats on the grid walk test at 4 weeks post-lesion and on the beam walk test at 2 weeks post-lesion.
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Animal Model:HAN: NMRI (female, 30-37 g, pregnant treated during gestational organogenesis)[3]
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Dosage:5 mg/kg (gestational day 8.25); 15 mg/kg (gestational day 8.25); 15 mg/kg (gestational day 11)
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Administration:p.o.; single dose
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Result:Induced 17% resorption rate, 9% cleft palate, 5% kidney hypoplasia, 11% hydronephrosis, 15% hydroureter, and increased fetal weight compared to controls at 5 mg/kg on gestational day 8.25.
Induced 17% resorption rate, 10% exencephaly, 42% cleft palate, 25% micrognathia, 10% exophthalmia, 6% anotia/microtia, 6% dark hemorrhagic liver, 10% atresia ani, 5% cleft mandible (in exencephalic fetuses), 5% tail malformation, 3% hydronephrosis, 3% urinary bladder aplasia, and increased fetal weight compared to controls at 15 mg/kg on gestational day 8.25.
Induced 9.8% resorption rate, 90.1% cleft palate, 8.1% micrognathia, 4.5% kidney hypoplasia, 9% hydronephrosis, 62.3% fetal limb malformations (54.1% hindlimb defects, 12.6% forelimb defects), 28.8% malformed mandible, 38.7% abnormal fusion of sternobrae, skeletal limb defects including malformed humerus, short radius/ulna/tibia, and bent/short/absent fibula, and increased fetal weight compared to controls at 15 mg/kg on gestational day 11.
Chemical Information
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CAS. Nr. 143984-56-9
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Molecular Weight 374.47
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Formel C25H26O3
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SMILES
O=C(C1=CC2=CC=C(C3=CC(C4(CCCCC4)C)=C(OC)C=C3)C=C2C=C1)O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Boisvieux-Ulrich E, et al. Differential effects of several retinoid receptor-selective ligands on squamous differentiation and apoptosis in airway epithelial cells. Cell and tissue research. 2000 Apr;300(1):67-81. [Content Brief]
[2]. Agudo M, et al. A retinoic acid receptor beta agonist (CD2019) overcomes inhibition of axonal outgrowth via phosphoinositide 3-kinase signalling in the injured adult spinal cord. Neurobiology of disease. 2010 Jan;37(1):147-55. [Content Brief]
[4]. Arafa HM, et al. Selective agonists of retinoic acid receptors: comparative toxicokinetics and embryonic exposure. Archives of toxicology. 2000 Jan;73(10-11):547-56. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
CD2019 Related Classifications
HY-183405 Related Classifications
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- CD2019
- 143984-56-9
- CD 2019
- CD-2019
- RAR/RXR
- squamous differentiation
- pregnant NMRI mice
- PI3K signalling
- RARβ
- primary rabbit tracheal epithelial cells
- post-natal day 3 rat pup cerebellar neurons
- PI3K/Akt signalling pathway
- cervical dorsal column spinal cord lesions
- retinoic acid receptor beta
- squamous metaplasia
- Inhibitor
- inhibitor
- inhibit