Stemolecule™ PD0325901

PD0325901 is a small molecule targeting mitogen-activated protein kinase (MAPK/ERK kinase or MEK) with potential antineoplastic activity. PD0325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation^1,2. Along with the ALK5 inhibitor SB431542, PD0325901 has also been shown to increase the efficiency of reprogramming human primary fibroblasts into induced pluripotent stem (iPS) cells³.

Stemgent and the Stemolecule brand name are trademarks of REPROCELL Inc., Japan.

Product Name: Stemolecule PD0325901

Catalog Number: 04-0006

Size

• 2 mg (Cat. No. 04-0006)
• 10 mg (Cat. No. 04-0006-10)
• 2 mg in 10 mM DMSO (Cat. No. 04-0006-02)

Alternate Name(s): N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-benzamide

Chemical Formula: C₁₆H₁₄F₃IN₂O₄

Molecular Weight: 482.19

CAS Number: 391210-10-9

Purity: Greater than 95 % by HPLC analysis

Formulation: Pale purple solid

Solubility: Reconstitute in DMSO to the desired concentration. For reconstitution instructions please reference product specifications sheet.

Storage and Stability: Store powder at 4 °C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C, protected from light. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of PD0325901 was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. No acute cytotoxicity was observed in mouse embryonic stem cells following a 6 hour exposure to 1 nM — 100µm of PD0325901.

Handling: Before opening, briefly centrifuge the vial to ensure full recovery of sample. Aliquotting the stock solution is recommended to avoid repetitive freeze-thaw cycles. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%.

Specification Sheets:

• 04-0006 Specifications Sheet
• 04-0006-10 Specifications Sheet
• 04-0006-02 Specifications Sheet

Safety Data Sheets:

• 04-0006 and 04-0006-10 Safety Data Sheet
• 04-0006-02 Safety Data Sheet

1. Bain, J., Plater, L., Elliott, M., Hastie, C.J., McLauchlan, H., Klevernic, I., Arthur, J.S., Alessi, D.R., and Cohen, P. The selectivity of protein kinase inhibitors: a further update. Biochem J 408: 297-315 (2007).
2. Sebolt-Leopold, J.S. and Herrera, R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4: 937-947 (2004).
3. Lin, T., Ambasudhan, R., Yuan, X., Li, W., Hilcove, S., Abujarour, R., Lin, X., Hahm, H.S., Hao, E., Hayek, A., and Ding, S. A chemical platform for improved induction of human iPSCs. Nat Methods 6: 805-808 (2009).

Additional Publications

• Lowe MG; Yen M-R; Hsu F-M; Hoshhama L; Hu Z; Chitiashvili T; Hunt TJ; Gorgy I; Bernard M; Wanaitha SE; Chen P-Y; Clark AT. EED is required for mouse primordial germ cell differentiation in the embryonic gonad. Developmental Cell 57:1482.e5 (2022).
• Zijlmans DW; Talon I; Verhelst S; Benda;; A' Van Nerum K; Javali A; Malcolm AA; van Knippenbeg SSFA; Biggins L ;To SK; Janiszewski A; Admiraal D; Knops R; Corthlut N; Balaton B; Georgolopoulos G; Panda A; Bhanu NV; Collier AJ; Fabian C; Allso[ RN; Chappell J; Pham TXA; Oberhuemer M; Ertekin C; Vanheer L; Athanasouli P; Lluis F; Deforce D; Jansen JH; Garcia BA; Vermeulen M; Rifron N; Dhaenens M; Marks H; Rugg-Gunn PJ; Pasque V. Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction. Nature Cell Biol 25:858 (2022).
• Klaus A; Clapes T; Yvernogeau L; Basu S; Veijts B; Maas J; Smal I; Galjart N; Robin C. CLASP2 safeguards hematopoietic stem cell properties during mouse and fish development. Cell Rep 39:110957 (2022).
• Choi J; Chen W; Minkina A; Chardon FM; Suiter CC; Regalado SG; Domcke S; Hamazaki N; Lee C; Martin B; Daza RM; Shendure J. A time-resolved, multi-symbol molecular recorder via sequential genome editing. Nature 508:98 (2022).
• Ishikura T; Ohta H; Nagano M; Saitou M. Optimized protocol to derive germline stem-cell-like cells from mouse pluripotent stem cells. Star Protocols 3:101544 (2022).
• Tian L; Zhang X-h; Xu ;K Li Y. Induced pluripotent stem cell line BIOi003-A from a patient with ABCA4-associated retinal dystrophy carrying compound heterozygous c.(1222C>T;2919-884G>T) variants in ABCA4. Stem Cell Res 64:102894 (2022).
• Gonzàlez BJ; Zhao H; Niu J; Williams DJ; Lee J; Goulbourne CN' Xing Y; Wang Y' Oberholzer J; Blumenkrantz MH; Chen X; LeDuc CA; Chung WK; Colecraft HM; Gromada J; ShenY; Goland RS; Leibel RL; Egli D. Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency. Commun Biology 5:779 (2022).
• Clarke R; Terry AR; Pennington H; Hasty C; MacDougall MS; Regan M; Merrill BJ. Sequential Activation of Guide RNAs to Enable Successive CRISPR-Cas9 Activities. Molecular Cell 81:226023800000 (2021).
• Mori Y; Takashima S; Kanatsu-Shinohara M; Yi Z; Shinohara T. Cdc42 is required for male germline niche development in mice. Cell Rep 36:109550 (2021).
• Huang X; Park K; Gontarz P Zhang B; Pan J; McKenzie Z; Fischer LA; Dong C; Dietmann S; Xing X; Shliaha PB; Yang J; Li D; Ding J; Lungjangwa T; Mitalipova M; Khan S; Imsoonthornruksa S; Jensen M; Wang T; Kadoch C; Raenisch R; Wang J; Theunissen TW. OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human. Nature Commun 12:5123 (2021).
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• Teleahmad S' Salari A; Samadian A' Chee SH' Hwang D' Lee B'; Bayarsaikjan D; Bayarsaikjan G; Lee J; Park JH; Hassani S-N; Baharvand H; Salekdeh GH. BMP4 signaling plays critical roles in self-renewal of R2i mouse embryonic stem cells. Biochem Biophys Res Commun 617:1-8 (2022).
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• Wang S-H; Wang X-P. Generation of an induced pluripotent stem cell (iPSC) line (THSJTUi001-A) from a Wilson's disease patient harboring a homozygous Arg778Leu mutation in ATP7B gene. Stem Cell Res 49:102050 (2020).
• Coyne AN; Zaepfel BL; Hayes L; Fitchman B; Salzberg Y; Luo E-C; Bowen K; Trost H; Aigner S; Rigo F; Yeo GW; Harel A; Csvendsen CN; Sareen D; Rothstein JD. G₄C₂ Repeat RNA Initiates a POM121-Mediated Reduction in Specific Nucleoporins in C9orf72 ALS/FTD. Neuron 107:1124-1140.e11 (2020).
• Shan H; Ye J; Zhuang T; TIanRui H; HaiPing X; ShengSheng Z; XinYue H; HanYu L; Lun W; ShuYang Z. Establishment of an induced pluripotent stem cell line PUMCHi004-A from a hereditary transthyretin amyloid cardiomyopathy patient with transthyretin (TTR) p.Asp38Asn mutation. Stem Cell Res :102022 (2020).
• Shen H; Ye J; Ping XH; Yue HX; Yang ZS. Establishment of an induced pluripotent stem cell line from a patient with hereditary transthyretin amyloidosis carrying transthyretin (TTR) mutation p.Phe53Val. Stem Cell Res https://doi.org/10.1016/j.scr.2020.101940: (2020).
• Li CH; Coffey EL; Dall'Agnese A; Hannett NM; Tang X; Henninger JE; Platt JM; Oksuz O; Zamudio AV; Afeyan LK; Schuijers J; Liu XS; Markoulaki S; Lungjangwa T; LeRoy G; Svoboda DS; Wogram E; Lee TI; Jaenisch R; Young RA. MeCP2 links heterochromatin condensates and neurodevelopmental disease. Nature :doi.org/10.1038/s41586-020-2574-4 (2020).
• Long P; Liu Z; Wu B; Chen J; Sun C; Wang F; Huang Y; Chen H; Li Q; Ma Y. Generation of an induced pluripotent stem cell line from chorionic villi of a Patau syndrome spontaneous abortion. Stem Cell Res 45:101789 (2020).
• Liu Y; Cheng J; Siejka-Zelińska P; Weldon C; Roberts H; Lopopolo M; Magri A; D'Arienzo V; Harris JM; McKeating JA; Song C-X. Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS. Genome Biol 21:54 (2020).
• Georges A; Takeda H; Lavergne A; Mandai M; Lepiemme F; Karim L; Memeulenaere L; Schyns M; Nguyen L; Rakic J-M; Takahashi M; Georges M. Combined analysis of single cell RNA-Seq and ATAC-Seq data reveals regulatory toggles operating in native and iPS-derived retina. bioRxiv :https://doi.org/10.1101/2020.03.02.972497 (2020).
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• Zhang Y; Zhang Y; Li M; Mend F; Yu Z; Chen Y; Cui G. Combination of SB431542, CHIR99021 and PD0325901 has a synergic effect on abrogating valproic acid‑induced epithelial‑mesenchymal transition and stemness in HeLa, 5637 and SCC‑15 cells. Oncol Rep In Press:https://doi.org/10.3892/or.2019.7088 (2019).
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• Goto T; Hara ; Sanbo M; Masaki H; Sato H; Yamaguchi T; Hochi S; Kobayashi T; Nakauchi H; Hirabayashi M. Generation of pluripotent stem cell-derived mouse kidneys in Sall1-targeted anephric rats. Nature Commun 10:451 (2019).
• Saldaña-Meyer R; Rodriguez-Hemaez J; Nishana M; Jácome-López K; Nora EP; Bruneau BG; Furlan-Magaril M; Skok J; Reinberg D. RNA interactions with CTCF are essential for its proper function. bioRxiv :http://dx.doi.org/10.1101/530014.  (2019).
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• Zaidan NZ; Walker KJ; Brown JE; Schaffer LV; Scalf M; Shortreed MR; Iyer G; Smith LM; Sridharan R. Compartmentailzaton of HP1 proteins in pluripotency acquisition and maintenance. Stem Cell Reports 10:627 (2018).
• Wang X; Sterr M; Burtscher I; CHen S; Hieronimus A; Machicao F; Staiger H; Haring H-U; Lederer G; Irmler M; Bechers J; de Angelis MH; Ray M; Wright CVE; Bakhti M; Lickert H. Genome-wide analysis of PDX1 target genes in human pancreatic progenitors. Mol Metab 9:57-68 (2018).
• McCracken KW; Aihara E; Martin B; Crawford CM; Broda T; Treguier J; Zhang X; Shannon JM; Montrose MH; Wells JM. Wnt/β-catenin promotes gastric fundus specification in mice and humans. Nature 541:182-187 (2017).
• Lin Y; Linask KL; Mallon B; Johnson K; Kleni M; Beers J; Xie W; Du Y; Liu C; Lai Y; Zou J; Haigney M; Yang H; Rao M; Chen G. Heparin Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-free Medium, Enabling Consistent Manufacture of Cardiomyocytes. Stem Cells Translat Med 6:527-538 (2017).
• Goolam M; Zernicka-Goetz M. The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo. Development 144:1450-1461 (2017).
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• Zimmerlan L; Park TS; Huo JS; Verma K; Pather SR; Talbot CC; Agarwal J; Steppan D; Zhang YW; Considine M; Guo H; Zhong X; Gutierrez C; Cope L; Canto-Soler MV; Friedman AD; Baylin SB; Zambdis ET. Tankyrase inhibition promotes a stable human naive pluripotent state with improved functionality. Development 2016:dev.138982 (2016).
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• Higuchi S; Watanabe TM; Kawauchi K; Ichimura T; Fujita H. Culturing of mouse and human cells on soft substrates promote the expression of stem cell markers. J Biosci Bioeng 117:749 (2014).
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