A1632-100mg | SB202190 (FHPI) [152121-30-7] Biotrend

Background

SB202190 (FHPI) is a potent p38 MAPK inhibitor that specifically inhibits p38α and p38β with IC50 values of 50 and 100 nM, respectively [1].

SB202190 has been reported to potently enhance the growth of leukemia cell lines THP-1 and MV4-11. SB202190 activates the phosphorylation ERK and C-Raf. Studies have shown that the ED50 values of U0126 and FPT inhibitor II were significantly decreased in the presence of SB202190 [2].

SB202190 triggers changes in cell cycle profiles both during HU treatment and caffeine-induced PCC (premature chromosome condensation) in plants. Moreover, SB202190 and caffeine decrease independently HU-induced histone H4 Lys5 acetylation [3].

References:
[1] Davies SP1, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1; 351 (Pt 1): 95-105.
[2] Hirosawa M1, Nakahara M, Otosaka R, Imoto A, Okazaki T, Takahashi S. The p38 pathway inhibitor SB202190 activates MEK/MAPK to stimulate the growth of leukemia cells. Leuk Res. 2009 May; 33 (5): 693-9.
[3] Winnicki K1, Maszewski J. SB202190 affects cell response to hydroxyurea-induced genotoxic stress in root meristems of Vicia faba. Plant Physiol Biochem. 2012 Nov; 60: 129-36.

Product Citation

1. Jingchun Du, Yougui Xiang, et al. "RIPK1 dephosphorylation and kinase activation by PPP1R3G/PP1γ promote apoptosis and necroptosis." Nat Commun. 2021 Dec 3;12(1):7067. PMID: 34862394
2. Bas Ponsioen, Jasmin B Post, et al. "Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling." Nat Cell Biol. 2021 Apr;23(4):377-390. PMID: 33795873
3. Tong Wang, Qi Sun, et al. "A1 Reactive Astrocytes Activated by 2-chloroethanol Modulate M1 Microglia Polarization through Upregulating IL-1β and TNF-α." Research Square. April 13th, 2021
4. Tong Wang, Qi Sun, et al. "A1 astrocytes activated by 2-Chloroethanol via the ROS-induced p38 MAPK/NF-κB and AP-1 pathways modulate microglia polarization." Research Square. April 12th, 2021.
5. Shuxian Wang, Qiwei Chen, et al. "Omega-3 polyunsaturated fatty acids alleviate hydrogen sulfide-induced blood-testis barrier disruption in the testes of adult mice." Reprod Toxicol. 2020 Oct 14;S0890-6238(20)30233-1. PMID: 33068716
6. Post JB, Hami N, et al. "CRISPR-induced RASGAP deficiencies in colorectal cancer organoids reveal that only loss of NF1 promotes resistance to EGFR inhibition." Oncotarget. 2019 Feb 15;10(14):1440-1457. PMID: 30858928
7. van der Waals LM, Laoukili J, et al. "Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures." Sci Rep. 2019 Jan 28;9(1):819. PMID: 30692572
8. Ramos-Alvarez I, Lee L, et al. "Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of Na(+),K(+)-ATPase in pancreatic acinar cells." Am J Physiol Gastrointest Liver Physiol. 2019 Feb 1;316(2):G263-G277. PMID: 30520694
9. Ramos-Alvarez I, Jensen RT. "P21-activated kinase 4 in pancreatic acinar cells is activated by numerous gastrointestinal hormones/neurotransmitters and growth factors by novel signaling, and its activation stimulates secretory/growth cascades." Am J Physiol Gastrointest Liver Physiol. 2018 Aug 1;315(2):G302-G317. PMID: 29672153
10. Verissimo CS, Overmeer RM, et al. "Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening." Elife. 2016 Nov 15;5. pii: e18489. PMID: 27845624

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Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	331.34
Cas No.	152121-30-7
Formula	C₂₀H₁₄N₃OF
Solubility	insoluble in H2O; ≥22.47 mg/mL in EtOH; ≥57.7 mg/mL in DMSO
Chemical Name	4-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl)phenol
SDF	Download SDF
Canonical SMILES	OC1=CC=C(C2=NC(C3=CC=C(F)C=C3)=C(C4=CC=NC=C4)N2)C=C1
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment[1]:
Cell lines	THP-1 and MV4-11 leukemia cells
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reacting condition	72 h, 5 μM
Applications	SB202190 is a specific inhibitor of p38ɑ and p38β through competition with ATP for the same binding site on p38. SB202190 potently activated the growth of THP-1 and MV4-11 cells. Furthermore, SB202190 increased the phosphorylation of C-Raf and ERK, suggesting that Raf–MEK–MAPK pathway activation is involved in the cell growth induced by SB202190.
Animal experiment [2]:
Animal models	Three-month specific pathogen-free (SPF) male Wistar rats
Dosage form	5 μL of 10 μmol/L SB202190, ICV injection
Application	One week after SB202190 treatment, p38 MAPK phosphorylation in hippocampus was higher in the model group than in the SB202190 group. Compared to the model group, the SB202190 group exhibited significantly shorter escape latencies in the Morris water maze hidden platform trials. The SB202190 group also showed higher Bcl-2 expression, lower caspase-3 expression and significantly decreased neuronal apoptosis in hippocampus.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Hirosawa M, Nakahara M, Otosaka R, et al. The p38 pathway inhibitor SB202190 activates MEK/MAPK to stimulate the growth of leukemia cells [J]. Leukemia research, 2009, 33 (5): 693-699. [2] Yang S, Zhou G, Liu H, et al. Protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a rat model of vascular dementia [J]. BioMed research international, 2013, 2013: 215798.

Biological Activity

Description	SB202190 is a highly selective, potent and cell-permeable inhibitor of p38 MAP kinases with IC50 values of 50 nM and 100 nM for p38α and p38β, respectively.
Targets	p38α MAPK	p38β MAPK
IC50	50 nM	100 nM