CID-755673 | CAS#521937-07-5 | PKD inhibitor

MedKoo Cat#: 406532 | Name: CID-755673

Description:

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

CID-755673 is a selective protein kinase D (PKD) inhibitor. CID-755673 was identified from the National Institutes of Health small molecule repository library of 196,173 compounds. In cell-based assays, CID755673 blocked phorbol ester-induced endogenous PKD1 activation in LNCaP cells in a concentration-dependent manner. CID755673 inhibited prostate cancer cell proliferation, cell migration, and invasion. In summary, our findings indicate that CID755673 is a potent and selective PKD1 inhibitor with valuable pharmacological and cell biological potential.

Chemical Structure

CID-755673

CAS#521937-07-5

Theoretical Analysis

MedKoo Cat#: 406532

Name: CID-755673

CAS#: 521937-07-5

Chemical Formula: C12H11NO3

Exact Mass: 217.0739

Molecular Weight: 217.22

Elemental Analysis: C, 66.35; H, 5.10; N, 6.45; O, 22.10

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	2 Weeks

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Related CAS #

No Data

Synonym

CID755673; CID 755673; CID-755673.

IUPAC/Chemical Name

7-hydroxy-2,3,4,5-tetrahydro-1H-benzofuro[2,3-c]azepin-1-one

InChi Key

AACFPJSJOWQNBN-UHFFFAOYSA-N

InChi Code

InChI=1S/C12H11NO3/c14-7-3-4-10-9(6-7)8-2-1-5-13-12(15)11(8)16-10/h3-4,6,14H,1-2,5H2,(H,13,15)

SMILES Code

O=C1NCCCC2=C1OC3=CC=C(O)C=C32

Appearance

brown 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, not in water

Shelf Life

>2 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#BBC70303

QC Data

View QC data: current batch, Lot#BBC70303

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CID755673 is a potent PKD inhibitor with IC50s of 182 nM, 280 nM and 227 nM for PKD1, PKD2 and PKD3, respectively.

In vitro activity:

Since the finding that cell treatment with CID755673 strikingly enhanced [3H]thymidine incorporation in response to multiple agonists was unexpected, it was determined whether the stimulatory effect of this compound reflects an increase in DNA replication through the S phase of the cell cycle rather than an increase in the transport and/or phosphorylation of [3H]thymidine. Consequently, flow cytometric analysis was used to determine the proportion of cells in the various phases of the cell cycle. As shown in Fig. 4, addition of 25 μM CID755673 strikingly increased the movement from G1 to S and G2 plus M induced by bombesin, EGF or PDBu in Swiss 3T3 cells. Thus, CID755673 markedly stimulated progression through the cell cycle induced by growth-promoting stimuli that act either through PKD1-dependent (e.g. bombesin, PDBu) or PKD1-independent (e.g. EGF) signaling pathways in Swiss 3T3 cells. Reference: Biochem Biophys Res Commun. 2010 Jan 1; 391(1): 63–68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812606/

In vivo activity:

db/db mice were administered vehicle or CID755673 at 1 or 10mg/kg body weight by daily i.p. injection for two weeks. CID755673 had no effect on body weight or fasting blood glucose, but did induce a dose-dependent decrease in gross heart weight and heart weight when normalised to tibia length (Fig. 4A). CID755673 administered at 10mg/kg increased heart rate when compared with vehicle (Fig. 4A). Echocardiographic assessment of heart structure and function by M-mode and Doppler imaging (Fig. 4B) showed that CID755673 administration at 10mg/kg reduced LV posterior wall (LVPW) thickness at diastole when compared with both vehicle and 1mg/kg CID755673 administration regimens (Fig. 4C). CID755673 administered at both doses reduced LV internal diameter (LVID) at systole. No other differences in LV morphology at either diastole or systole were observed with CID755673 administration. However, CID755673 administration at 10mg/kg enhanced both diastolic function, signified by an increased E:A ratio (Fig. 4D) and reduced deceleration time (Fig. 4E), and systolic function, demonstrated by decreased ejection time (Fig. 4F). Dose-dependent increases in indices of systolic function, such as ejection fraction (Fig. 4G) and fractional shortening (Fig. 4H) were also observed. Together, these data show that the PKD inhibitor CID755673 enhanced both diastolic and systolic cardiac function in db/db mice, which was associated with a reduction in gross heart weight and reduced LVID at systole. Reference: PLoS One. 2015; 10(3): e0120934. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370864/

	Solvent	mg/mL	mM
Solubility
	DMSO	46.0	211.77

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 217.22 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. Torres-Marquez E, Sinnett-Smith J, Guha S, Kui R, Waldron RT, Rey O, Rozengurt E. CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway. Biochem Biophys Res Commun. 2010 Jan 1;391(1):63-8. doi: 10.1016/j.bbrc.2009.11.002. Epub 2009 Nov 5. PMID: 19896460; PMCID: PMC2812606. 2. Sharlow ER, Giridhar KV, LaValle CR, Chen J, Leimgruber S, Barrett R, Bravo-Altamirano K, Wipf P, Lazo JS, Wang QJ. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem. 2008 Nov 28;283(48):33516-26. doi: 10.1074/jbc.M805358200. Epub 2008 Sep 30. PMID: 18829454; PMCID: PMC2586241. 3.Venardos K, De Jong KA, Elkamie M, Connor T, McGee SL. The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS One. 2015 Mar 23;10(3):e0120934. doi: 10.1371/journal.pone.0120934. PMID: 25798941; PMCID: PMC4370864. 4. Wang W, Duclot F, Groveman BR, Carrier N, Qiao H, Fang XQ, Wang H, Xin W, Jiang XH, Salter MW, Ding XS, Kabbaj M, Yu XM. Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats. PLoS One. 2018 Apr 3;13(4):e0195095. doi: 10.1371/journal.pone.0195095. PMID: 29614089; PMCID: PMC5882104.

In vitro protocol:

In vivo protocol:

1.Venardos K, De Jong KA, Elkamie M, Connor T, McGee SL. The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS One. 2015 Mar 23;10(3):e0120934. doi: 10.1371/journal.pone.0120934. PMID: 25798941; PMCID: PMC4370864. 2. Wang W, Duclot F, Groveman BR, Carrier N, Qiao H, Fang XQ, Wang H, Xin W, Jiang XH, Salter MW, Ding XS, Kabbaj M, Yu XM. Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats. PLoS One. 2018 Apr 3;13(4):e0195095. doi: 10.1371/journal.pone.0195095. PMID: 29614089; PMCID: PMC5882104.

1: Talman V, Gateva G, Ahti M, Ekokoski E, Lappalainen P, Tuominen RK. Evidence for a role of MRCK in mediating HeLa cell elongation induced by the C1 domain ligand HMI-1a3. Eur J Pharm Sci. 2014 May 13;55:46-57. doi: 10.1016/j.ejps.2014.01.002. Epub 2014 Jan 29. PubMed PMID: 24486483. 2: Scheiter M, Bulitta B, van Ham M, Klawonn F, KÃ¶nig S, JÃ¤nsch L. Protein Kinase Inhibitors CK59 and CID755673 Alter Primary Human NK Cell Effector Functions. Front Immunol. 2013 Mar 18;4:66. doi: 10.3389/fimmu.2013.00066. eCollection 2013. PubMed PMID: 23508354; PubMed Central PMCID: PMC3600540. 3: Mansky KC, Jensen ED, Davidova J, Yamamoto M, Gopalakrishnan R. Protein kinase D promotes in vitro osteoclast differentiation and fusion. J Biol Chem. 2013 Apr 5;288(14):9826-34. doi: 10.1074/jbc.M112.444133. Epub 2013 Feb 21. PubMed PMID: 23430742; PubMed Central PMCID: PMC3617283. 4: Uesugi A, Kataoka A, Tozaki-Saitoh H, Koga Y, Tsuda M, Robaye B, Boeynaems JM, Inoue K. Involvement of protein kinase D in uridine diphosphate-induced microglial macropinocytosis and phagocytosis. Glia. 2012 Jul;60(7):1094-105. doi: 10.1002/glia.22337. Epub 2012 Apr 4. PubMed PMID: 22488958. 5: Yuan J, Liu Y, Tan T, Guha S, Gukovsky I, Gukovskaya A, Pandol SJ. Protein kinase d regulates cell death pathways in experimental pancreatitis. Front Physiol. 2012 Mar 27;3:60. doi: 10.3389/fphys.2012.00060. eCollection 2012. PubMed PMID: 22470346; PubMed Central PMCID: PMC3313474. 6: George KM, Frantz MC, Bravo-Altamirano K, Lavalle CR, Tandon M, Leimgruber S, Sharlow ER, Lazo JS, Wang QJ, Wipf P. Design, Synthesis, and Biological Evaluation of PKD Inhibitors. Pharmaceutics. 2011;3(2):186-228. doi: 10.3390/pharmaceutics3020186. PubMed PMID: 22267986; PubMed Central PMCID: PMC3261798. 7: Bravo-Altamirano K, George KM, Frantz MC, Lavalle CR, Tandon M, Leimgruber S, Sharlow ER, Lazo JS, Wang QJ, Wipf P. Synthesis and Structure-Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D. ACS Med Chem Lett. 2011 Feb 14;2(2):154-159. PubMed PMID: 21617763; PubMed Central PMCID: PMC3100199. 8: Pilankatta R, Lewis D, Inesi G. Involvement of protein kinase D in expression and trafficking of ATP7B (copper ATPase). J Biol Chem. 2011 Mar 4;286(9):7389-96. doi: 10.1074/jbc.M110.171454. Epub 2010 Dec 27. PubMed PMID: 21189263; PubMed Central PMCID: PMC3044995. 9: Lavalle CR, Bravo-Altamirano K, Giridhar KV, Chen J, Sharlow E, Lazo JS, Wipf P, Wang QJ. Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility. BMC Chem Biol. 2010 May 5;10:5. doi: 10.1186/1472-6769-10-5. PubMed PMID: 20444281; PubMed Central PMCID: PMC2873968. 10: Torres-Marquez E, Sinnett-Smith J, Guha S, Kui R, Waldron RT, Rey O, Rozengurt E. CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway. Biochem Biophys Res Commun. 2010 Jan 1;391(1):63-8. doi: 10.1016/j.bbrc.2009.11.002. Epub 2009 Nov 5. PubMed PMID: 19896460; PubMed Central PMCID: PMC2812606.