BDP9066 | CAS#2226507-04-4 | MRCK Inhibitor

MedKoo Cat#: 563970 | Name: BDP9066

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

BDP9066

CAS#2226507-04-4

Theoretical Analysis

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

Price and Availability

Size	Price	Availability
1mg	USD 80.00	Ready to ship
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship
100mg	USD 1,650.00	Ready to ship

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Related CAS #

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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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YXM210222

QC Data

View QC data: current batch, Lot#YXM210222

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

BDP9066 is a potent and selective myotonic dystrophy-related Cdc42-binding kinase MRCK inhibitor with an IC50 of 64 nM for MRCKβ in SCC12 cells, Ki values of 0.0136 nM and 0.0233 nM for MRCKα/β in house determinations, respectively.

In vitro activity:

To investigate the effect of BDP9066 on pMLC2 in SCC12 cells, which express MRCK but no detectable DMPK (Supplemental Figure 5), varying BDP9066 concentrations incubated with cells for 2 hours led to dose-dependent inhibition of MLC2 phosphorylation (Figure 6A, left) with an EC50 = 64 nM (Figure 6A, right), corresponding to a 5-fold increase in cellular potency relative to BDP5290 (19). SCC12 cell viability following 24 hour treatment was unaffected by all BDP9066 concentrations up to 0.5 µM (Figure 6B), despite maximal pMLC2 inhibition at this concentration (Figure 6A), with a 25% decrease in viability at 1 μM (Figure 6B). These results indicate that BDP9066 is relatively non-toxic at concentrations that profoundly inhibit substrate phosphorylation. Treatment of SCC12 cells with non-toxic 0.5 μM BDP9066 led to changes in cell morphology, with reduced proportions of regularly (rounded, few protrusions) shaped cells (Figure 6C, green cells), and increased irregularly (greater spreading, increased protrusions) shaped cells (Figure 6C, blue cells) as determined by high content imaging. The collective effect of these BDP9066 induced morphological alterations resulted in increased 2D cell area and decreased roundness (Figure 6E, right panels). In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells Reference: Cancer Res. 2018 Apr 15; 78(8): 2096–2114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901721/

In vivo activity:

BDP9066 was evaluated for in vivo pharmacological proof-of-concept as an SCC chemotherapeutic agent. Topical application of 25 µg BDP9066 on FVB mouse skin twice per day for 2 days led to 26 µM mean BDP9066 concentration in skin, but only 0.04 µM in blood (Figure 7A). BDP9066 application led to significantly reduced epidermal MRCKα pS1003 positive staining (Figure 7B). To determine how repeated dosing would affect BDP9066 accumulation and distribution, skin and blood concentrations were determined after 10 μg was administered once, or 25 μg was repeated over 4 days (Figure 7C). Although relative to the single 10 μg dose, repeated 25 μg doses did result in 2.8 fold higher concentrations in skin (Figure 7C, left panel), and 4 fold higher concentrations in blood (Figure 7C, right panel), these differences were less than the 10 fold difference in total BDP9066 administered, indicating that compound accumulation was less than additive. These results indicated that 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. Reference: Cancer Res. 2018 Apr 15; 78(8): 2096–2114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901721/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	10.0	28.70

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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

Formulation protocol:

1. 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-172870. Epub 2018 Jan 30. PMID: 29382705; PMCID: PMC5901721. 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.

In vitro protocol:

In vivo protocol:

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.