Table 3. Inhibition of selected kinases in vitro by small molecule BMP inhibitors.
Results of in vitro kinases assays for ALK1-6, BMPR2, TGF-β type II receptor (TGFR2) and VEGF receptor (KDR) are shown as IC50 (concentration at 50 % inhibition). IC50s for in vitro kinase assay are not identical with the published IC50s for cell based studies described in the text. *Results obtained by CCH, which may vary from published reports based on experimental conditions. n.d.: not determine. NO: no inhibition at highest concentration tested (>30–100 μM).
| IC50 (nM) | Dorsomorphin (DM)* [140] | LDN-193189 [145, 157] | DMH1* [158] | DMH2* [158] | DMH3* [158] | ML347* [144] | K02288 [145] | LDN-212854* [159] | LDN-214117 [146] |
|---|---|---|---|---|---|---|---|---|---|
| ALK1 | 100 | 1 | 25 | 10 | 5 | 45 | 2 | 55 | 27 |
| ALK2 | 60 | 1 | 100 | 40 | 25 | 30 | 1 | 15 | 27 |
| ALK3 | 95 | 5 | <5 | <5 | <5 | >10000 | 34 | 120 | 1171 |
| ALK6 | 230 | 17 | 48 | <5 | 10 | >9000 | 6 | 220 | 3000 |
| ALK4 | >20000 | 100 | >9000 | 1400 | 640 | NO | 302 | >9000 | n.d. |
| ALK5 | >17000 | 350 | NO | 2400 | 2000 | NO | 321 | >11000 | n.d. |
| BMPR2 | 70 | n.d. | NO | >3800 | 2200 | NO | n.d. | n.d. | n.d. |
| TGFR2 | 100 | n.d. | NO | 86 | 246 | NO | n.d. | n.d. | n.d. |
| KDR | 20 | 556 | NO | 2400 | 2000 | >19000 | >10000 | 2770 | n.d. |