CRT0066101 | CAS#956121-30-5 | PRKDs inhibitor

MedKoo Cat#: 408135 | Name: CRT0066101 free base

Description:

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

CRT0066101 is a PRKDs inhibitor. CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer. CRT0066101 treatment or PKD2 silencing arrested bladder cancer cells at the G2/M phase, the arrest being accompanied by decreases in the levels of cyclin B1, CDK1 and phospho-CDK1 (Thr161) and increases in the levels of p27Kip1 and phospho-CDK1 (Thr14/Tyr15). CRT0066101 suppresses bladder cancer growth by inhibiting PKD2 through induction of G2/M cell cycle arrest, leading to the blockade of cell cycle progression.

Chemical Structure

CRT0066101 free base

CAS#956121-30-5 (free base)

Theoretical Analysis

MedKoo Cat#: 408135

Name: CRT0066101 free base

CAS#: 956121-30-5 (free base)

Chemical Formula: C18H19ClN4O

Exact Mass: 342.1247

Molecular Weight: 342.83

Elemental Analysis: C, 63.06; H, 5.59; Cl, 10.34; N, 16.34; O, 4.67

Price and Availability

Size	Price	Availability
25mg	USD 350.00	2 Weeks
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,950.00	2 Weeks
2g	USD 6,950.00	2 Weeks

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Related CAS #

956121-30-5 (free base) 1883545-60-5 (HCl)

Synonym

CRT-0066101; CRT 0066101; CRT0066101 free base

IUPAC/Chemical Name

2-[4-[[(2R)-2-Aminobutyl]amino]-2-quinazolinyl]-4-chloro-phenol

InChi Key

OC1=CC=C(Cl)C=C1C2=NC(NC[C@H](N)CC)=C3C=CC=CC3=N2

InChi Code

InChI=1S/C18H19ClN4O/c1-2-12(20)10-21-17-13-5-3-4-6-15(13)22-18(23-17)14-9-11(19)7-8-16(14)24/h3-9,12,24H,2,10,20H2,1H3,(H,21,22,23)/t12-/m1/s1

SMILES Code

OC1=CC=C(Cl)C=C1C2=NC(NC[C@H](N)CC)=C3C=CC=CC3=N2

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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

Instruction

View handling instruction

Biological target:

CRT0066101 is a potent and specific PKD inhibitor with IC50 values of 1, 2.5 and 2 nM for PKD1, 2, and 3 respectively.

In vitro activity:

The time-course of CRT0066101 suppression of the proliferation of the four cell lines was characterized in vitro using the MTT assay. All of the four cell lines examined showed a maximal inhibitory effect at day 4 following CRT0066101 treatment (Fig. 2a). Reference: Cell Mol Life Sci. 2018 Mar; 75(5): 939–963. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984729/

In vivo activity:

Treatment of mice with CRT0066101 did result in a significant decrease of primary tumor size and weight (Fig. 5A, Supplemental Fig. S9), associated with an approximately 50% decrease in tumor cell proliferation (Fig. 5B), and an increase of apoptosis (Fig. 5C). Reference: Mol Cancer Ther. 2015 Jun; 14(6): 1306–1316. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458391/

Preparing Stock Solutions

The following data is based on the product molecular weight 342.83 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. Liu Y, Wang Y, Yu S, Zhou Y, Ma X, Su Q, An L, Wang F, Shi A, Zhang J, Chen L. The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer. Cell Physiol Biochem. 2019;52(3):382-396. doi: 10.33594/000000027. Epub 2019 Mar 8. PMID: 30845378. 2. Li QQ, Hsu I, Sanford T, Railkar R, Balaji N, Sourbier C, Vocke C, Balaji KC, Agarwal PK. Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M. Cell Mol Life Sci. 2018 Mar;75(5):939-963. doi: 10.1007/s00018-017-2681-z. Epub 2017 Oct 25. PMID: 29071385; PMCID: PMC7984729. 3. Borges S, Perez EA, Thompson EA, Radisky DC, Geiger XJ, Storz P. Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101. Mol Cancer Ther. 2015 Jun;14(6):1306-16. doi: 10.1158/1535-7163.MCT-14-0945. Epub 2015 Apr 7. PMID: 25852060; PMCID: PMC4458391.

In vitro protocol:

In vivo protocol:

1. Li QQ, Hsu I, Sanford T, Railkar R, Balaji N, Sourbier C, Vocke C, Balaji KC, Agarwal PK. Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M. Cell Mol Life Sci. 2018 Mar;75(5):939-963. doi: 10.1007/s00018-017-2681-z. Epub 2017 Oct 25. PMID: 29071385; PMCID: PMC7984729. 2. Borges S, Perez EA, Thompson EA, Radisky DC, Geiger XJ, Storz P. Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101. Mol Cancer Ther. 2015 Jun;14(6):1306-16. doi: 10.1158/1535-7163.MCT-14-0945. Epub 2015 Apr 7. PMID: 25852060; PMCID: PMC4458391.

1: Liu Y, Zhou Y, Ma X, Chen L. Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple-Negative Breast Cancer Tumor Growth. Adv Sci (Weinh). 2021 Jan 6;8(4):2003205. doi: 10.1002/advs.202003205. PMID: 33643800; PMCID: PMC7887572. 2: Armacki M, Polaschek S, Waldenmaier M, Morawe M, Ruhland C, Schmid R, Lechel A, Tharehalli U, Steup C, Bektas Y, Li H, Kraus JM, Kestler HA, Kruger S, Ormanns S, Walther P, Eiseler T, Seufferlein T. Protein Kinase D1, Reduced in Human Pancreatic Tumors, Increases Secretion of Small Extracellular Vesicles From Cancer Cells That Promote Metastasis to Lung in Mice. Gastroenterology. 2020 Sep;159(3):1019-1035.e22. doi: 10.1053/j.gastro.2020.05.052. Epub 2020 May 22. PMID: 32446697. 3: Leightner AC, Mello Guimaraes Meyers C, Evans MD, Mansky KC, Gopalakrishnan R, Jensen ED. Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases. Int J Mol Sci. 2020 Feb 5;21(3):1056. doi: 10.3390/ijms21031056. PMID: 32033440; PMCID: PMC7036879. 4: Cho H, Bhatti FU, Hasty KA, Yi AK. Nanosome-Mediated Delivery Of Protein Kinase D Inhibitor Protects Chondrocytes From Interleukin-1β-Induced Stress And Apoptotic Death. Int J Nanomedicine. 2019 Nov 11;14:8835-8846. doi: 10.2147/IJN.S218901. PMID: 31806974; PMCID: PMC6857658. 5: Lieb WS, Lungu C, Tamas R, Berreth H, Rathert P, Storz P, Olayioye MA, Hausser A. The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple- negative breast cancer stem cells. Int J Cancer. 2020 Jun 15;146(12):3423-3434. doi: 10.1002/ijc.32798. Epub 2019 Dec 14. PMID: 31745977. 6: Liu Z, Wang Y, Pan S, Zhang Y, Zhu H, Liu Y, Zhu L, Zhang J. Platelets- released insulin-like growth factor 1 is correlated with anxiety in myocardial infarction. Biochem Biophys Res Commun. 2019 Dec 3;520(2):441-448. doi: 10.1016/j.bbrc.2019.10.042. Epub 2019 Oct 10. PMID: 31607475. 7: Zhao P, Pattison LA, Jensen DD, Jimenez-Vargas NN, Latorre R, Lieu T, Jaramillo JO, Lopez-Lopez C, Poole DP, Vanner SJ, Schmidt BL, Bunnett NW. Protein kinase D and Gβγ mediate sustained nociceptive signaling by biased agonists of protease-activated receptor-2. J Biol Chem. 2019 Jul 5;294(27):10649-10662. doi: 10.1074/jbc.RA118.006935. Epub 2019 May 29. PMID: 31142616; PMCID: PMC6615677. 8: Martínez-León E, Amable G, Jácamo R, Picco ME, Anaya L, Rozengurt E, Rey O. Protein kinase D1 inhibition interferes with mitosis progression. J Cell Physiol. 2019 Nov;234(11):20510-20519. doi: 10.1002/jcp.28651. Epub 2019 Apr 17. PMID: 30997696. 9: Liu Y, Wang Y, Yu S, Zhou Y, Ma X, Su Q, An L, Wang F, Shi A, Zhang J, Chen L. The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer. Cell Physiol Biochem. 2019;52(3):382-396. doi: 10.33594/000000027. Epub 2019 Mar 8. PMID: 30845378. 10: Sutton JA, Rogers LM, Dixon BREA, Kirk L, Doster R, Algood HM, Gaddy JA, Flaherty R, Manning SD, Aronoff DM. Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus. Am J Reprod Immunol. 2019 Mar;81(3):e13075. doi: 10.1111/aji.13075. Epub 2019 Jan 30. PMID: 30582878; PMCID: PMC6459189. 11: Yuan J, Tan T, Geng M, Tan G, Chheda C, Pandol SJ. Novel Small Molecule Inhibitors of Protein Kinase D Suppress NF-kappaB Activation and Attenuate the Severity of Rat Cerulein Pancreatitis. Front Physiol. 2017 Dec 7;8:1014. doi: 10.3389/fphys.2017.01014. PMID: 29270134; PMCID: PMC5725929. 12: Plastira I, Bernhart E, Goeritzer M, DeVaney T, Reicher H, Hammer A, Lohberger B, Wintersperger A, Zucol B, Graier WF, Kratky D, Malle E, Sattler W. Lysophosphatidic acid via LPA-receptor 5/protein kinase D-dependent pathways induces a motile and pro-inflammatory microglial phenotype. J Neuroinflammation. 2017 Dec 19;14(1):253. doi: 10.1186/s12974-017-1024-1. PMID: 29258556; PMCID: PMC5735906. 13: Li QQ, Hsu I, Sanford T, Railkar R, Balaji N, Sourbier C, Vocke C, Balaji KC, Agarwal PK. Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M. Cell Mol Life Sci. 2018 Mar;75(5):939-963. doi: 10.1007/s00018-017-2681-z. Epub 2017 Oct 25. PMID: 29071385. 14: Hao F, Xu Q, Zhao Y, Stevens JV, Young SH, Sinnett-Smith J, Rozengurt E. Insulin Receptor and GPCR Crosstalk Stimulates YAP via PI3K and PKD in Pancreatic Cancer Cells. Mol Cancer Res. 2017 Jul;15(7):929-941. doi: 10.1158/1541-7786.MCR-17-0023. Epub 2017 Mar 30. PMID: 28360038; PMCID: PMC5645013. 15: Guedán A, Swieboda D, Charles M, Toussaint M, Johnston SL, Asfor A, Panjwani A, Tuthill TJ, Danahay H, Raynham T, Mousnier A, Solari R. Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication. J Virol. 2017 Apr 13;91(9):e00217-17. doi: 10.1128/JVI.00217-17. PMID: 28228588; PMCID: PMC5391474. 16: Wang J, Sinnett-Smith J, Stevens JV, Young SH, Rozengurt E. Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells: A NOVEL ROLE FOR PROTEIN KINASE D (PKD). J Biol Chem. 2016 Aug 19;291(34):17988-8005. doi: 10.1074/jbc.M115.711275. Epub 2016 Jul 1. PMID: 27369082; PMCID: PMC5016186. 17: Jensen DD, Zhao P, Jimenez-Vargas NN, Lieu T, Gerges M, Yeatman HR, Canals M, Vanner SJ, Poole DP, Bunnett NW. Protein Kinase D and Gβγ Subunits Mediate Agonist-evoked Translocation of Protease-activated Receptor-2 from the Golgi Apparatus to the Plasma Membrane. J Biol Chem. 2016 May 20;291(21):11285-99. doi: 10.1074/jbc.M115.710681. Epub 2016 Mar 30. PMID: 27030010; PMCID: PMC4900274. 18: Kim do Y, Park EY, Chang E, Kang HG, Koo Y, Lee EJ, Ko JY, Kong HK, Chun KH, Park JH. A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer. Oncotarget. 2016 Mar 22;7(12):14791-802. doi: 10.18632/oncotarget.7443. PMID: 26895471; PMCID: PMC4924752. 19: Coughlan KA, Valentine RJ, Sudit BS, Allen K, Dagon Y, Kahn BB, Ruderman NB, Saha AK. PKD1 Inhibits AMPKα2 through Phosphorylation of Serine 491 and Impairs Insulin Signaling in Skeletal Muscle Cells. J Biol Chem. 2016 Mar 11;291(11):5664-5675. doi: 10.1074/jbc.M115.696849. Epub 2016 Jan 21. PMID: 26797128; PMCID: PMC4786706. 20: Borges S, Perez EA, Thompson EA, Radisky DC, Geiger XJ, Storz P. Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101. Mol Cancer Ther. 2015 Jun;14(6):1306-16. doi: 10.1158/1535-7163.MCT-14-0945. Epub 2015 Apr 7. PMID: 25852060; PMCID: PMC4458391.