BTT-3033

• CAT Number: R064176
• CAS Number: 1259028-99-3
• Molecular Formula: C23H20FN5O3S
• Molecular Weight: 465.50
• Purity: ≥95%
• Synonyms: 1-[4-[[1-(4-fluorophenyl)pyrazol-4-yl]sulfonyl-methylamino]phenyl]-3-phenylurea
• InChI: InChI=1S/C23H20FN5O3S/c1-28(33(31,32)22-15-25-29(16-22)21-11-7-17(24)8-12-21)20-13-9-19(10-14-20)27-23(30)26-18-5-3-2-4-6-18/h2-16H,1H3,(H2,26,27,30)
• InChIKey: NSLIQOPYDUKWTA-UHFFFAOYSA-N
• SMILES: CN(C1=CC=C(C=C1)NC(=O)NC2=CC=CC=C2)S(=O)(=O)C3=CN(N=C3)C4=CC=C(C=C4)F

BTT-3033 is an orally active conformation-selective inhibitor of α2β1 (EC50: 130 nM) by binding to the α2I domain. BTT-3033 inhibits platelet binding to collagen Ⅰ and cell proliferation, and induces cell apoptosis. BTT-3033 can be used in the research of prostate cancer, inflammation and cardiovascular disease[1][2][4].
BTT-3033 (1 nM-100 μM, 2 h) inhibits CHO-α2wt cell adhesion to rat tail collagen Ⅰ (EC50: 130 nM), exhibits selectivity for α2β1 over α3β1, α4β1, α5β1 and αv[1].
BTT-3033 (10 μM, 5 min) inhibits human platelet binding to collagenⅠcoated capillaries under flow, with the EC50 value for mouse whole blood to be 6 μM[1].
BTT-3033 (10 μM, 5 min) inhibits binding of α2-expressing CHO cells to collagen Ⅰ under shear stress conditions[1].
BTT-3033 (1 μM, 60 min) inhibits of neurogenic and thromboxane A2‐induced human prostate smooth muscle contraction[3].
BTT-3033 (25 and 50 μM, 48 h) inhibits cell viability and proliferation by inducing G1 cell cycle arrest in LNcap‐FGC, and DU‐145 cells[4].
BTT-3033 (50 μM, 48 h) induces apoptosis through the activation of ROS, Bax protein upregulation, caspase‐3 activation, and depletion of ΔΨm[4].
BTT-3033 (10 μM, 15/28 days) suppresses MMP13 expression, increases the expression of MMP1 and MT-MMP1 in human articular cartilage‑derived chondrocytes[5].
BTT-3033 (oral administration, 10 mg/kg, at 24 h and 2 h before PAF induction) shows anti-inflammatory effects in mouse air pouch model[2].
BTT-3033 (oral administration, 10 mg/kg, at 48 ,24 and 2 h before ear swelling) shows anti-inflammatory effects in arachidonic acid-induced ear edema model[2].

Reference

[1]. Liisa Nissinen, et al. Novel α2β1 integrin inhibitors reveal that integrin binding to collagen under shear stress conditions does not require receptor preactivation. J Biol Chem. 2012 Dec 28;287(53):44694-702.
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[2]. Liisa Nissinen, et al. Sulfonamide inhibitors of α2β1 integrin reveal the essential role of collagen receptors in in vivo models of inflammation. Pharmacol Res Perspect. 2015 Jun;3(3):e00146.
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[3]. Bingsheng Li, et al. Inhibition of neurogenic and thromboxane A 2 -induced human prostate smooth muscle contraction by the integrin α2β1 inhibitor BTT-3033 and the integrin-linked kinase inhibitor Cpd22. Prostate. 2020 Aug;80(11):831-849.
 [Content Brief]

[4]. Zahra Salemi, et al. Integrin α2β1 inhibition attenuates prostate cancer cell proliferation by cell cycle arrest, promoting apoptosis and reducing epithelial-mesenchymal transition. J Cell Physiol. 2021 Jul;236(7):4954-4965.
 [Content Brief]

[5]. Takashi Kanamoto, et al. Integrin α2β1 plays an important role in the interaction between human articular cartilage-derived chondrocytes and atelocollagen gel. Sci Rep. 2021 Jan 19;11(1):1757.
 [Content Brief]