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MedKoo CAT#: 563970
CAS#: 2226507-04-4
Description: BDP9066 is a potent and selective MRCK inhibitor with an IC50 of 64 nM for MRCKβ in SCC12 cells, Ki values of 0.0136 nM . BDP9066 reduced substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. BDP-9066 prevented radiation-driven increases in motility both in vitro and in a clinically relevant orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in combination with RT significantly increased survival in this model and markedly reduced infiltration of the contralateral cerebral hemisphere.
MedKoo Cat#: 563970
Name: BDP9066
CAS#: 2226507-04-4
Chemical Formula: C20H24N6
Exact Mass: 348.2062
Molecular Weight: 348.45
Elemental Analysis: C, 68.94; H, 6.94; N, 24.12
BDP9066 is in stock. The same day shipping after order is received.
Synonym: BDP9066; BDP-9066; BDP 9066
IUPAC/Chemical Name: (S)-8-(3-(Pyrimidin-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1,8-diazaspiro[5.5]undecane
InChi Key: UELSMLDRSQFVHG-FQEVSTJZSA-N
InChi Code: InChI=1S/C20H24N6/c1-2-8-25-20(6-1)7-3-11-26(13-20)17-5-10-22-19-18(17)15(12-23-19)16-4-9-21-14-24-16/h4-5,9-10,12,14,25H,1-3,6-8,11,13H2,(H,22,23)/t20-/m0/s1
SMILES Code: N(CCC1)(C2=C3C(NC=C3C4=NC=NC=C4)=NC=C2)C[C@@]51CCCCN5
| Biological target: | IC50 of 64 nM for MRCKβ in SCC12 cells, Ki values of 0.0136 nM |
|---|---|
| In vitro activity: | BDP9066 is a potent and highly selective inhibitors of MRCK with robust on-target actions in vitro and in whole cells. BDP9066 inhibits MLC phosphorylation and blocks SCC12 squamous cell carcinoma motility and invasion. In SCC12 cells BDP9066 potently inhibits MRCK at sub-micromolar levels, leading to inhibition of MLC phosphorylation, changes in cell morphology, and reduced cell motility and 3D collagen invasion, without significantly affecting cell viability. Reference: Cancer Res. 2018 Apr 15;78(8):2096-2114. |
| In vivo activity: | It was possible to achieve sustainable BDP9066 levels in mouse skin by repeated topical application, which were sufficient to induce phenotypic responses in squamous cell carcinoma cells in vitro, without significant compound accumulation following sequential administration. BDP9066 are valuable chemical biology tools to identify MRCK biological functions and roles in cancer, and that MRCK inhibition has in vivo therapeutic effects on skin cancer in mice. Reference: Cancer Res. 2018 Apr 15;78(8):2096-2114. |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| Soluble in DMSO | 10.0 | 28.7 |
The following data is based on the product molecular weight 348.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | Unbekandt M, Belshaw S, Bower J, Clarke M, Cordes J, Crighton D, Croft DR, Drysdale MJ, Garnett MJ, Gill K, Gray C, Greenhalgh DA, Hall JAM, Konczal J, Lilla S, McArthur D, McConnell P, McDonald L, McGarry L, McKinnon H, McMenemy C, Mezna M, Morrice NA, Munro J, Naylor G, Rath N, Schüttelkopf AW, Sime M, Olson MF. Discovery of Potent and Selective MRCK Inhibitors with Therapeutic Effect on Skin Cancer. Cancer Res. 2018 Apr 15;78(8):2096-2114. doi: 10.1158/0008-5472.CAN-17-2870. Epub 2018 Jan 30. PMID: 29382705; PMCID: PMC5901721. |
| In vivo protocol: | Unbekandt M, Belshaw S, Bower J, Clarke M, Cordes J, Crighton D, Croft DR, Drysdale MJ, Garnett MJ, Gill K, Gray C, Greenhalgh DA, Hall JAM, Konczal J, Lilla S, McArthur D, McConnell P, McDonald L, McGarry L, McKinnon H, McMenemy C, Mezna M, Morrice NA, Munro J, Naylor G, Rath N, Schüttelkopf AW, Sime M, Olson MF. Discovery of Potent and Selective MRCK Inhibitors with Therapeutic Effect on Skin Cancer. Cancer Res. 2018 Apr 15;78(8):2096-2114. doi: 10.1158/0008-5472.CAN-17-2870. Epub 2018 Jan 30. PMID: 29382705; PMCID: PMC5901721. |
1: Kurimchak AM, Herrera-Montávez C, Brown J, Johnson KJ, Sodi V, Srivastava N, Kumar V, Deihimi S, O'Brien S, Peri S, Mantia-Smaldone GM, Jain A, Winters RM, Cai KQ, Chernoff J, Connolly DC, Duncan JS. Functional proteomics interrogation of the kinome identifies MRCKA as a therapeutic target in high-grade serous ovarian carcinoma. Sci Signal. 2020 Feb 18;13(619):eaax8238. doi: 10.1126/scisignal.aax8238. PMID: 32071169; PMCID: PMC7294993.
2: Birch JL, Strathdee K, Gilmour L, Vallatos A, McDonald L, Kouzeli A, Vasan R, Qaisi AH, Croft DR, Crighton D, Gill K, Gray CH, Konczal J, Mezna M, McArthur D, Schüttelkopf AW, McConnell P, Sime M, Holmes WM, Bower J, McKinnon HJ, Drysdale M, Olson MF, Chalmers AJ. A Novel Small-Molecule Inhibitor of MRCK Prevents Radiation-Driven Invasion in Glioblastoma. Cancer Res. 2018 Nov 15;78(22):6509-6522. doi: 10.1158/0008-5472.CAN-18-1697. Epub 2018 Oct 2. PMID: 30279244.
3: Unbekandt M, Belshaw S, Bower J, Clarke M, Cordes J, Crighton D, Croft DR, Drysdale MJ, Garnett MJ, Gill K, Gray C, Greenhalgh DA, Hall JAM, Konczal J, Lilla S, McArthur D, McConnell P, McDonald L, McGarry L, McKinnon H, McMenemy C, Mezna M, Morrice NA, Munro J, Naylor G, Rath N, Schüttelkopf AW, Sime M, Olson MF. Discovery of Potent and Selective MRCK Inhibitors with Therapeutic Effect on Skin Cancer. Cancer Res. 2018 Apr 15;78(8):2096-2114. doi: 10.1158/0008-5472.CAN-17-2870. Epub 2018 Jan 30. PMID: 29382705; PMCID: PMC5901721.
