VEGFR/PDGFR/CA II-IN-1
VEGFR/PDGFR/CA II-IN-1 is a VEGFR/PDGFR/CA II inhibitor. VEGFR/PDGFR/CA II-IN-1 potently inhibits VEGFR2 (IC50 = 62.66 nM), PDGFRα (IC50 = 18.65 nM), PDGFRβ (IC50 = 5.23 nM), and hCA II (Ki = 19.4 nM), with weaker activity against hCA I (Ki = 154.2 nM) and hCA IX (Ki = 121.0 nM). VEGFR/PDGFR/CA II-IN-1 exhibits potent antiproliferative activity in VEGFR2-BAF3 cells and robust inhibition of angiogenesis in human umbilical vein endothelial cells (HUVECs). VEGFR/PDGFR/CA II-IN-1 inhibits the formation of corneal neovascularization in rabbits through multiple signaling pathways, and significantly reduced intraocular pressure (IOP) in both acute and chronic glaucoma models. VEGFR/PDGFR/CA II-IN-1 can be used to study neovascular glaucoma (NVG).
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- CAS No.: 3099422-14-4
- Formula: C36H35FN6O6S
- Molecular Weight:698.76
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
VEGFR2 62.66 nM (IC50) |
PDGFRα 18.65 nM (IC50) |
PDGFRβ 5.23 nM (IC50) |
hCA II 19.4 nM (Ki) |
hCA I 154.2 nM (Ki) |
hCA IX 121.0 nM (Ki) |
In Vitro
VEGFR/PDGFR/CA II-IN-1 (compound H24) exhibits good enzyme inhibitory activities against both VEGFR2 and hCA II, with inhibition rates of 63.75% and 91.53% at 100 nM[1].
VEGFR/PDGFR/CA II-IN-1 (48 h) demonstrates favorable safety profiles in ARPE-19 and HCE-T cells[1].
VEGFR/PDGFR/CA II-IN-1 exhibits potent inhibition of VEGFR2 (IC50 = 62.66 nM) and hCA II (Ki = 19.4 nM), along with superior selectivity for hCA II over hCA I (Ki = 154.2 nM; SI = 7.9) and hCA IX (Ki = 121.0 nM; SI = 6.2)[1].
VEGFR/PDGFR/CA II-IN-1 (3 days) exhibits potent antiproliferative activity against VEGFR2-BAF3 cells with an IC50 of 75.2 nM, demonstrating favorable activity at the cellular level[1].
VEGFR/PDGFR/CA II-IN-1 (3-12 h) demonstrates dose-dependent inhibition of angiogenesis in HUVECs, with superior inhibitory effects on vessel length and junction number at 1 μM compared to the positive control Vorolanib (HY-109019)[1].
VEGFR/PDGFR/CA II-IN-1 exhibits strong inhibitory activity against VEGFR and PDGFR families while showing minimal inhibition against TIE2 (Inhibition% = −3.90% at 500 nM), and demonstrates potent activity against PDGFRα (IC50 = 18.65 nM) and PDGFRβ (IC50 = 5.23 nM), which is stronger than that of Vorolanib, confirming its profile as an efficient VEGFR/PDGFR/CA II dual-functional inhibitor[1].
VEGFR/PDGFR/CA II-IN-1 (500 nM; 60min) exhibits strong inhibitory activity against VEGFR and PDGFR families while showing minimal inhibition against TIE2 (Inhibition% = −3.90% at 500 nM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | T1/2 (Plasma) | T1/2 | Clearance (CL) |
|---|---|---|---|---|---|
| Mice[1] | 0.5 μg/kg | o.a. | >990 min | 21.4 min | 64.8 L/min/kg |
In Vivo
VEGFR/PDGFR/CA II-IN-1 (0.5 mg/kg; subconjunctival injection; single dose) exhibits lower conjunctival irritation than the Vorolanib and ACZ combination groups, as evidenced by significantly lower IL-1β levels and no obvious redness or swelling at 12 h post-administration, while also demonstrating a significant IOP-lowering effect in the acute glaucoma rabbit model[1].
VEGFR/PDGFR/CA II-IN-1 (0.5 mg/kg; subconjunctival injection; once every 5 days; 15 days) demonstrates a significant IOP-lowering effect in the chronic glaucoma rabbit model[1].
VEGFR/PDGFR/CA II-IN-1 (0.5 mg/kg; subconjunctival injection; single dose) achieves robust intraocular drug accumulation while minimizing systemic exposure in rabbit in vivo eye tissue distribution experiment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Japanese white rabbits, weighing 1.8-2.2 kg, were anesthetized with urethane and proparacaine hydrochloride eye drops, subjected to corneal alkali burn by applying a 5 mm filter paper soaked in 1 M NaOH for 30 s, followed by immediate removal and rinsing of the ocular surface and subconjunctival sac with 100 mL of physiological saline[1].
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Dosage:0.5 mg/kg
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Administration:subconjunctival injection; once every 5 days; 15 days
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Result:Showed that the area of corneal neovascularization in the treated group was significantly lower than that in the model group.
Reduced the area of corneal neovascularization to 77.8% and 65.7% of the model group value at 14 and 21 days after alkali treatment, respectively, demonstrating similar inhibitory efficacy to Vorolanib at both time points.
Decreased the density of new blood vessels in the cornea, with a slightly lower vascular density than that observed in the Vorolanib group and the combination groups.
Reduced the vascular lumen area in the cornea compared with the model group, showing comparable lumen area reduction to Vorolanib, while the combination groups exhibited significantly larger lumen areas than H24 alone significantly.
Exhibited a much stronger inhibitory effect on corneal neovascularization than the combination of Vorolanib and ACZ, as evidenced by smaller vascular areas and lumen areas in the H24-treated group compared with the combination groups at all time points.
Inhibited the phosphorylation of VEGFR2 and PDGFRβ in rabbit corneas, as confirmed by Western blot analysis effectively.
Reduced the overexpression of FAK in rabbit corneas without altering AQP1 expression levels.
Attenuated the interaction between AQP1 and FAK, as demonstrated by Co-IP analysis significantly.
Reduced the expression of FAK, p-PI3K, and p-AKT, indicating that H24 inhibited the activation of the FAK-PI3K/AKT signaling pathway effectively.
Inhibited the phosphorylation of FAK and Paxillin, confirming its role in modulating the VEGFR2/FAK signaling pathway effectively.
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Animal Model:Male Japanese white rabbits, weighing 1.8-2.2 kg, were placed in rabbit boxes with their heads secured, anesthetized with 15% urethane and locally with proparacaine hydrochloride eye drops, and then injected with 0.05 mL of hypertonic sodium chloride solution (10% NaCl in distilled water) into the aqueous humor of both eyes, followed by anti-inflammatory treatment with ofloxacin ointment[1].
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Dosage:0.5 mg/kg
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Administration:subconjunctival injection; single dose
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Result:Decreased IOP by 29.0 mmHg within 0-120 min after administration in the acute glaucoma model.
Further reduced IOP by 8.8 mmHg during the 120-180 min period, demonstrating a continued IOP-lowering effect.
Achieved an IOP reduction rate of 41.7% during the 120-180 min interval, which was superior to that of ACZ (22.2%) and the combination groups (24.6% and 27.9%), indicating that H24 exhibited a better IOP-lowering effect at 2 h after administration.
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Animal Model:Male Japanese white rabbits, weighing 1.8-2.2 kg, were placed in rabbit boxes with their heads fixed, anesthetized with 20% urethane (5 mL/kg) and locally with proparacaine hydrochloride eye drops, injected with 0.05 mL of compound carbomer solution into the anterior chamber of the eye, and then treated with ofloxacin ointment for anti-inflammation[1].
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Dosage:0.5 mg/kg
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Administration:subconjunctival injection; once every 5 days; 15 days
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Result:Decreased IOP by 6.3 mmHg on the seventh day compared with the model group, demonstrating a good IOP-lowering effect comparable to that of ACZ (6.8 mmHg).
Demonstrated a similar IOP-lowering effect to that of ACZ with the increase in administration frequency, and after the 17th day, the ΔIOP values of H24 were even lower than those of ACZ.
Administered alone exhibited a slightly better IOP-lowering effect than the combination of Vorolanib and ACZ.
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Animal Model:Male Japanese white rabbit (1.8-2.2 kg)[1].
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Dosage:0.5 mg/kg
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Administration:subconjunctival injection; single dose
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Result:Distributed from the conjunctiva to the sclera, cornea, iris-ciliary body complex, and retina gradually. Reached its maximum concentration in the sclera (6.27 μg/mL) at 3 h after administration.
Peaked in the cornea at 12 h (3.58 μg/mL), and maintained a detectable concentration of 2.55 μg/mL at 48 h after administration.
Remained below 0.01 μg/mL in the retina within the first 3 h, but increased to 0.29 μg/mL at 12 h and remained detectable at 0.17 μg/mL at 48 h, indicating effective penetration into the retina.
Reached its maximum concentration in the iris-ciliary body complex (2.10 μg/mL) at 12 h and remained at 1.13 μg/mL at 48 h.
Exhibited low systemic exposure after subconjunctival administration, with plasma concentrations of only 0.32 μg/mL at 3 h and below 0.01 μg/mL at 12 h.
Chemical Information
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CAS No. 3099422-14-4
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Molecular Weight 698.76
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Formula C36H35FN6O6S
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SMILES
O=C(C1=C(C)NC(/C=C2C(NC3=C\2C=C(F)C=C3)=O)=C1C)N[C@@H]4CN(C(CN(CC5=CC=CC=C5)C(C6=CC=C(S(=O)(N)=O)C=C6)=O)=O)CC4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VEGFR/PDGFR/CA II-IN-1 Related Classifications
HY-184656 Related Classifications
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