PD0407824
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406344

CAS#: 622864-54-4

Description: PD0407824, also known as PD407824 is a potent selective, small molecular CHK1 inhibitor with potential anticancer activity.

Chemical Structure

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PD0407824
CAS# 622864-54-4
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406344
Name: PD0407824
CAS#: 622864-54-4
Chemical Formula: C20H12N2O3
Exact Mass: 328.08
Molecular Weight: 328.327
Elemental Analysis: C, 73.16; H, 3.68; N, 8.53; O, 14.62

Price and Availability

Size Price Availability Quantity
5mg USD 275 2 Weeks
10mg USD 500 2 Weeks
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Synonym: PD0407824; PD-0407824; PD 0407824; PD407824; PD-407824; PD 407824

IUPAC/Chemical Name: 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione

InChi Key: IAUZTOZLTFSMIE-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H12N2O3/c23-11-6-7-14-13(8-11)16-15(21-14)9-12(10-4-2-1-3-5-10)17-18(16)20(25)22-19(17)24/h1-9,21,23H,(H,22,24,25)

SMILES Code: O=C1NC(C2=C1C3=C(C=C2C4=CC=CC=C4)NC5=C3C=C(O)C=C5)=O

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: 0 – 4 C for short term (weeks to 1 month) or -20 C for long terms (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly.

Drug Formulation: This drug may be formulated in DMSO or ethanol.

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:
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Biological target: PD 407824 is a checkpoint kinase Chk1 and WEE1 inhibitor with IC50s of 47 and 97 nM.
In vitro activity: PD407824 at 0.1, 0.5 and 2 µM reduced the relative proliferation of 4T1.2 cells (Fig. 5A), and the expression level of p-eIF2α was elevated in a dose-dependent manner (Fig. 5B). Furthermore, the scratch assay with 4T1.2 mammary tumor cells revealed that PD407824 suppressed cell motility by inhibiting the healing of the wounded area (Fig. 5C). In addition to its effect on tumor cells, PD407824 affects RAW264.7 pre-osteoclasts similarly to AZD7762. PD407824 at 0.1, 0.5 and 2 µM reduced the relative proliferation of RAW264.7 cells (Fig. 5G). In MC3T3 cells, PD407824 at 0.1 and 0.5 µM did not significantly alter the relative cell proliferation, although a higher dosage of 2 µM decreased the number of MC3T3 cells (Fig. 5H). Reference: Int J Oncol. 2018 Sep;53(3):1001-1012. https://pubmed.ncbi.nlm.nih.gov/30015873/
In vivo activity: One sample was from a placebo-treated mouse, and the other was from a mouse treated with the investigational drug candidate, PD407824, an inhibitor of checkpoint kinases. Mechanical testing and microCT images revealed that bone strength is improved by administration of PD407824. Collectively, this FE study supports the notion that mechanical weakening of the femur was observed in the tumor-invaded trabecular bone, and chemical agents such as PD407824 may potentially assist in preventing bone loss and bone fracture. Reference: Int J Orthop (Hong Kong). 2018;5(1):863-871. https://pubmed.ncbi.nlm.nih.gov/30505850/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.3 305.42
Ethanol 8.2 24.98

Preparing Stock Solutions

The following data is based on the product molecular weight 328.33 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.

Recalculate based on batch purity %
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. Wang L, Wang Y, Chen A, Jalali A, Liu S, Guo Y, Na S, Nakshatri H, Li BY, Yokota H. Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling. Int J Oncol. 2018 Sep;53(3):1001-1012. doi: 10.3892/ijo.2018.4481. Epub 2018 Jul 13. PMID: 30015873; PMCID: PMC6065446. 2. Jiang F, Liu S, Chen A, Li BY, Robling AG, Chen J, Yokota H. Finite Element Analysis of the Mouse Distal Femur with Tumor Burden in Response to Knee Loading. Int J Orthop (Hong Kong). 2018;5(1):863-871. Epub 2018 Feb 28. PMID: 30505850; PMCID: PMC6261479.
In vitro protocol: 1. Wang L, Wang Y, Chen A, Jalali A, Liu S, Guo Y, Na S, Nakshatri H, Li BY, Yokota H. Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling. Int J Oncol. 2018 Sep;53(3):1001-1012. doi: 10.3892/ijo.2018.4481. Epub 2018 Jul 13. PMID: 30015873; PMCID: PMC6065446.
In vivo protocol: 1. Jiang F, Liu S, Chen A, Li BY, Robling AG, Chen J, Yokota H. Finite Element Analysis of the Mouse Distal Femur with Tumor Burden in Response to Knee Loading. Int J Orthop (Hong Kong). 2018;5(1):863-871. Epub 2018 Feb 28. PMID: 30505850; PMCID: PMC6261479.

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1. Neurofibromatoses therapeutic agents and screening for same. By Fernandez-Valle, Cristina. From PCT Int. Appl. (2013), WO 2013138463 A1 20130919.

2. Methods of treating cancer via modulation of deoxythymidylate kinase (DTYMK) and checkpoint kinase-1 (CHK1). By Wong, Kwok-Kin; Liu, Yan. From PCT Int. Appl. (2013), WO 2013103836 A2 20130711.

3. Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 Ser935 phosphorylation. By Hermanson, Spencer B.; Carlson, Coby B.; Riddle, Steven M.; Zhao, Jing; Vogel, Kurt W.; Nichols, R. Jeremy; Bi, Kun. From PLoS One (2012), 7(8), e43580. ,

4. Exploring protein kinase inhibitors. Unveiling gemcitabine resistance in pancreatic cancer. Comments. By Kim, Yeon Jeong; Hong, Young Bin; Cho, Chi Heum; Seong, Yeon-Sun; Bae, Insoo. From Pancreas (Hagerstown, MD, United States) (2012), 41(5), 804-805. ,

5. Testing the Promiscuity of Commercial Kinase Inhibitors Against the AGC Kinase Group Using a Split-luciferase Screen. By Jester, Benjamin W.; Gaj, Alicia; Shomin, Carolyn D.; Cox, Kurt J.; Ghosh, Indraneel. From Journal of Medicinal Chemistry (2012), 55(4), 1526-1537. ,

6. Novel combinations including a CENP-E inhibitor as cancer treatments. By Weber, Barbara; Wooster, Richard F.. From PCT Int. Appl. (2011), WO 2011031308 A1 20110317.

7. Postprocessing of Protein-Ligand Docking Poses Using Linear Response MM-PB/SA: Application to Wee1 Kinase Inhibitors. By Wichapong, Kanin; Lawson, Michael; Pianwanit, Somsak; Kokpol, Sirirat; Sippl, Wolfgang. From Journal of Chemical Information and Modeling (2010), 50(9), 1574-1588.

8. RNAi screening of the kinome identifies modulators of cisplatin response in ovarian cancer cells. By Arora, Shilpi; Bisanz, Kristen M.; Peralta, Lourdes A.; Basu, Gargi D.; Choudhary, Ashish; Tibes, Raoul; Azorsa, David O.. From Gynecologic Oncology (2010), 118(3), 220-227.

9. A Coiled-Coil Enabled Split-Luciferase Three-Hybrid System: Applied Toward Profiling Inhibitors of Protein Kinases. By Jester, Benjamin W.; Cox, Kurt J.; Gaj, Alicia; Shomin, Carolyn D.; Porter, Jason R.; Ghosh, Indraneel. From Journal of the American Chemical Society (2010), 132(33), 11727-11735.

10. Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors. By Wichapong, Kanin; Lindner, Marc; Pianwanit, Somsak; Kokpol, Sirirat; Sippl, Wolfgang. From European Journal of Medicinal Chemistry (2009), 44(4), 1383-1395.

11. Improvement of multivariate image analysis applied to quantitative structure-activity relationship (QSAR) analysis. By using wavelet-principal component analysis ranking variable selection and least-squares support vector machine regression: QSAR study of checkpoint kinase WEE1 inhibitors. By Cormanich, Rodrigo A.; Goodarzi, Mohammad; Freitas, Matheus P.. From Chemical Biology & Drug Design (2009), 73(2), 244-252.

12. Computer Simulations Reveal a Novel Nucleotide-Type Binding Orientation for Ellipticine-Based Anticancer c-kit Kinase Inhibitors. By Thompson, Damien; Miller, Charlotte; McCarthy, Florence O.. From Biochemistry (2008), 47(39), 10333-10344.

13. Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases. By Smaill, Jeff B.; Baker, Edward N.; Booth, R. John; Bridges, Alexander J.; Dickson, James M.; Dobrusin, Ellen M.; Ivanovic, Ivan; Kraker, Alan J.; Lee, Ho H.; Lunney, Elizabeth A.; et al. From European Journal of Medicinal Chemistry (2008), 43(6), 1276-1296.

14. 3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA. By Yi, Ping; Fang, Xin; Qiu, Minghua. From European Journal of Medicinal Chemistry (2008), 43(5), 925-938. , DOI:10.1016/j.ejmech.2007.06.021

15. 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure-Activity Relationships for Chromophore Modification and Phenyl Ring Substitution. By Palmer, Brian D.; Thompson, Andrew M.; Booth, R. John; Dobrusin, Ellen M.; Kraker, Alan J.; Lee, Ho H.; Lunney, Elizabeth A.; Mitchell, Lorna H.; Ortwine, Daniel F.; Smaill, Jeff B.; et al. From Journal of Medicinal Chemistry (2006), 49(16), 4896-4911. , DOI:10.1021/jm0512591

16. Structure and Inhibition of the Human Cell Cycle Checkpoint Kinase, Wee1A Kinase. By Squire, Christopher J.; Dickson, James M.; Ivanovic, Ivan; Baker, Edward N.. From Structure (Cambridge, MA, United States) (2005), 13(4), 541-550.

17. Modified human Wee1 kinase, crystals of peptide/inhibitor complexes containing such modified Wee1, and methods of use in the design and screening of Wee1 modulators. By Baker, Edward Neill; Booth, Richard John; Kraker, Alan J.; Ortwine, Daniel Fred; Dickson, James Michael Jeremy; Ivanovic, Ivan; Squire, Christopher John. From U.S. Pat. Appl. Publ. (2005), US 20050037476 A1 20050217.

18. Preparation of pyrrolocarbazoles, benzofuroisoindoles, and azacyclopentafluorenes inhibitors of checkpoint kinases WEE1 and CHK1. By Booth, Richard John; Denny, William Alexander; Dobrusin, Ellen Myra; Kraker, Alan John; Mitchell, Lorna Helen; Smaill, Jeffrey Bruce; Thompson, Andrew Mark; Lee, Ho Huat; Mccarthy, Florence Oliver Joseph; Palmer, Brian Desmond. From PCT Int. Appl. (2003), WO 2003091255 A1 20031106.