DDR1-IN-2

SKU: orb1301819

Description

DDR1-IN-2 (7rh) is a potent and selective ATP-competitive inhibitor of Discoidin Domain Receptor 1 (DDR1), demonstrating an IC50 of 6.8 nM. This small molecule is a valuable research tool for investigating DDR1's role in fibrosis and oncology through in vitro and in vivo experimental models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1429617-90-2
• MW: 546.59
• Purity: >99.99% (May vary between batches)
• Formula: C₃₀H₂₉F₃N₆O
• SMILES: CCc1ccc(cc1C#Cc1cnc2ccnn2c1)C(=O)Nc1cc(CN2CCN(C)CC2)cc(c1)C(F)(F)F
• Target: Discoidin Domain Receptor (DDR)
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:1.5 mg/mL (2.74 mM);DMSO:18.33 mg/mL (33.54 mM)

Bioactivity

• Target IC50:
  DDR1:6.8 nM (cell free)|DDR2:101.4 nM (cell free)
• In Vivo:
  DDR1-IN-2 possessed good PK profiles, with oral bioavailabilities of 67.4% . The inhibition of DDR1 with DDR1-IN-2 showed striking efficacy in combination with chemotherapy in orthotopic xenografts and autochthonous pancreatic tumors where it significantly reduced DDR1 activation and downstream signaling, reduced primary tumor burden, and improved chemoresponse .
• In Vitro:
  DDR1-IN-2 inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 nM, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. It bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. It also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity . Pharmacologic inhibition of DDR1 with an ATP-competitive orally available small-molecule kinase inhibitor (DDR1-IN-2) abrogated collagen-induced DDR1 signaling in pancreatic tumor cells and consequently reduced colony formation and migration .
• Cell Research:
  Adherent Cells were plated in 96-well culture plates with a cell density of 3000-4000 cells/well and treated with indicated compounds by adding 100μL medium containing compounds of various concentrations on the second day. After 72-hour's treatment, MTT was added to each well and incubated for additional 4-5 hours, and the absorbance was measured on a microplate reader at 570nm. Cell growth inhibition was evaluated as the ratio of the absorbance of the sample to that of the control. The results are representative of at least 4 independent experiments .
• Animal Research:
  Compounds 7rh and 7rj were dissolved in mixed solvents (DMSO : EtOH:Cremophor EL : H2O = 2 : 4 : 4 : 90) as clear solution. The final concentrations were 2.5 mg/mL. Sprague Dawley (SD) rats (male, 4 animals per group) weighted 180~220g were injected intravenously or administrated orally at doses of 5 mg/kg (i.v.) or 25mg/kg (p.o.), respectively. After dose administration, 0.3 mL of the orbital blood was taken at 2.0 min, 10.0 min, 30.0 min, 1.0 h, 2.0 h, 3.0 h, 4.0 h, 6.0 h, 8.0 h, 12.0 h, 21.0 h, 24.0 h, 30.0 h, 36.0 h, 48.0 h, and 72.0 h. Samples were stored at -70℃ until shipment to the analytical laboratory and tested by HPLC/MS using propranolol as internal standard to measure the compound concentration in the blood .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

7rh, DiscoidinDomainReceptor, DiscoidinDomainReceptor(DDR), Discoidin Domain Receptor, Discoidin Domain Receptor (DDR), Inhibitor, inhibit, DDR, DDR1, DDR1 IN 2, DDR1IN2, DDR-1-IN-2, DDR1-IN-2, DDR1 inhibitor 7rh

Compound Identifiers

PubChem CID

71550931