WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406713
Description: Ro 31-8220 is a PKC-inhibitor, which inhibits stimulated fluid pinocytosis of human PMNs induced by the PKC-activators phorbol myristate acetate (PMA, IC50 = 1.35 x 10(-6) M) or diacylglycerols (OAG, diC8) by 95%. Ro-31-8220 showed the apoptotic effect on HL-60 cells, which was mediated by a well-characterized transduction process of apoptotic signals: i.e., mitochondrial cytochrome c efflux and the activation of caspase-3 in the cytosol. Moreover, the ability of Ro-31-8220 to induce apoptotic activation was completely inhibited by the over-expression of the apoptotic suppressor gene, Bcl-2, in the cells.
MedKoo Cat#: 406713
Name: RO31-8220 mesylate
Chemical Formula: C26H27N5O5S2
Molecular Weight: 553.65
Elemental Analysis: C, 56.40; H, 4.92; N, 12.65; O, 14.45; S, 11.58
Related CAS #: 138489-18-6 (mesylate) 125314-64-9 (free base)
Synonym: RO31-8220; RO 31-8220; RO31-8220; RO318220; RO-318220; RO 318220; RO31-8220 mesylate; Bisindolylmaleimide IX; BIM IX.
IUPAC/Chemical Name: 3-(3-(4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-1H-indol-1-yl)propyl carbamimidothioate methanesulfonate
InChi Key: SAWVGDJBSPLRRB-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H23N5O2S.CH4O3S/c1-29-13-17(15-7-2-4-9-19(15)29)21-22(24(32)28-23(21)31)18-14-30(11-6-12-33-25(26)27)20-10-5-3-8-16(18)20;1-5(2,3)4/h2-5,7-10,13-14H,6,11-12H2,1H3,(H3,26,27)(H,28,31,32);1H3,(H,2,3,4)
SMILES Code: NC(SCCCN1C=C(C2=C(C3=CN(C)C4=C3C=CC=C4)C(NC2=O)=O)C5=C1C=CC=C5)=N.CS(=O)(O)=O
Appearance: Yellow to orange 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
|Biological target:||Ro 31-8220 mesylate is a potent PKC inhibitor, with IC50s of 5, 24, 14, 27, 24 and 23 nM for PKCα, PKCβI, PKCβII, PKCγ, PKCε and rat brain PKC, respectively. Ro 31-8220 also significantly inhibits MAPKAP-K1b, MSK1, S6K1 and GSK3β (IC50s, 3, 8, 15, and 38 nM, respectively).|
|In vitro activity:||In this study Ro31-8220, a compound identified by CREB activity screening, possesses anti-melanogenic activity associated with reduced MITF expression, tyrosinase activity, and melanin accumulation. Previous studies have demonstrated phosphorylation-dependent regulation of tyrosinase catalytic activity by PKCβ 9. However, in line with the selectivity of Ro31-8220 for PKCα 16-18, Ro31-8220 did not appear to directly affect tyrosinase activity, but rather decrease of tyrosinase activity by Ro31-8220 resulted from reduced tyrosinase expression due to downregulation of MITF. Full activation of CREB target gene expression requires phosphorylation of CREB at Ser133 by PKA as well as the dephosphorylation and nuclear translocation of CRTCs. This study found that Ro31-8220-mediated suppression of MITF expression was independent of CREB phosphorylation but associated with inhibition of CRTC3 nuclear entry. In line with these, MITF expression was markedly induced in UV or cAMP-stimulated conditions and the inhibitory activity of Ro31-8220 under the basal conditions of melanogenesis was weaker than cAMP-stimulated conditions. Reference: Theranostics. 2020; 10(9): 4017–4029. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086364/|
|In vivo activity:||In addition, a topical application of aged murine skin with a PKNγ inhibitor, Ro31-8220 significantly delays HAL-mediated permeability barrier recovery in wild-type (CD44+/+) mouse skin (Fig. 6D). Most importantly, a sequential topical treatment regimen [consisting of small HA followed by large HA (HAS-»HAL)] not only increases keratinocyte proliferation/skin thickness but also upregulates differentiation in aged mouse skin (Table 4). Sequential HA (HAS-»HAL) treatment also fully restores the permeability barrier function in aged murine skin to that observed in young murine skin (Fig. 6E). Downregulation of ROK and PKNγ by treating the mouse skin with Y27632 and Ro31-8220, respectively greatly reduces sequential HA (HAS-»HAL)-mediated epidermal functions and permeability barrier recovery (Fig. 6F). Taken together, these findings suggest that RhoGTPase-regulated ROK and PKNγ are closely involved in aged mouse epidermal functions (e.g., proliferation, differentiation, and permeability barrier recovery) during HAL or HAS or sequential HA (HAS-»HAL) treatment. These findings suggest that new HA signaling-based therapies may possibly counteract aberrant HA-induced epidermal dysfunction and age-associated skin disease. Reference: J Dermatol Sci. 2013 Oct; 72(1): 32–44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775883/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|DMF:PBS (pH 7.2) (1:9)||0.1||0.18|
The following data is based on the product molecular weight 553.65 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. Kim JH, Hong AR, Kim YH, Yoo H, Kang SW, Chang SE, Song Y. JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression. Theranostics. 2020 Mar 4;10(9):4017-4029. doi: 10.7150/thno.41502. PMID: 32226536; PMCID: PMC7086364. 2. Haick JM, Brueggemann LI, Cribbs LL, Denning MF, Schwartz J, Byron KL. PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2017 Jun 1;312(6):L822-L834. doi: 10.1152/ajplung.00567.2016. Epub 2017 Mar 10. PMID: 28283479. 3. Bourguignon LY, Wong G, Xia W, Man MQ, Holleran WM, Elias PM. Selective matrix (hyaluronan) interaction with CD44 and RhoGTPase signaling promotes keratinocyte functions and overcomes age-related epidermal dysfunction. J Dermatol Sci. 2013 Oct;72(1):32-44. doi: 10.1016/j.jdermsci.2013.05.003. Epub 2013 Jun 5. PMID: 23790635; PMCID: PMC3775883. 4. Loweth JA, Svoboda R, Austin JD, Guillory AM, Vezina P. The PKC inhibitor Ro31-8220 blocks acute amphetamine-induced dopamine overflow in the nucleus accumbens. Neurosci Lett. 2009 May 15;455(2):88-92. doi: 10.1016/j.neulet.2009.03.012. Epub 2009 Mar 11. PMID: 19368852; PMCID: PMC2688659.|
|In vitro protocol:||1. Kim JH, Hong AR, Kim YH, Yoo H, Kang SW, Chang SE, Song Y. JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression. Theranostics. 2020 Mar 4;10(9):4017-4029. doi: 10.7150/thno.41502. PMID: 32226536; PMCID: PMC7086364. 2. Haick JM, Brueggemann LI, Cribbs LL, Denning MF, Schwartz J, Byron KL. PKC-dependent regulation of Kv7.5 channels by the bronchoconstrictor histamine in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2017 Jun 1;312(6):L822-L834. doi: 10.1152/ajplung.00567.2016. Epub 2017 Mar 10. PMID: 28283479.|
|In vivo protocol:||1. Bourguignon LY, Wong G, Xia W, Man MQ, Holleran WM, Elias PM. Selective matrix (hyaluronan) interaction with CD44 and RhoGTPase signaling promotes keratinocyte functions and overcomes age-related epidermal dysfunction. J Dermatol Sci. 2013 Oct;72(1):32-44. doi: 10.1016/j.jdermsci.2013.05.003. Epub 2013 Jun 5. PMID: 23790635; PMCID: PMC3775883. 2. Loweth JA, Svoboda R, Austin JD, Guillory AM, Vezina P. The PKC inhibitor Ro31-8220 blocks acute amphetamine-induced dopamine overflow in the nucleus accumbens. Neurosci Lett. 2009 May 15;455(2):88-92. doi: 10.1016/j.neulet.2009.03.012. Epub 2009 Mar 11. PMID: 19368852; PMCID: PMC2688659.|
1: Kim SY, Kim S, Kim JM, Jho EH, Park S, Oh D, Yun-Choi HS. PKC inhibitors RO 31-8220 and GÃ¶ 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. BMB Rep. 2011 Feb;44(2):140-5. doi: 10.5483/BMBRep.2011.44.2.140. PubMed PMID: 21345315.
2: Marmy-Conus N, Hannan KM, Pearson RB. Ro 31-6045, the inactive analogue of the protein kinase C inhibitor Ro 31-8220, blocks in vivo activation of p70(s6k)/p85(s6k): implications for the analysis of S6K signalling. FEBS Lett. 2002 May 22;519(1-3):135-40. PubMed PMID: 12023032.
3: Chepurny OG, Hussain MA, Holz GG. Exendin-4 as a stimulator of rat insulin I gene promoter activity via bZIP/CRE interactions sensitive to serine/threonine protein kinase inhibitor Ro 31-8220. Endocrinology. 2002 Jun;143(6):2303-13. PubMed PMID: 12021195; PubMed Central PMCID: PMC3500996.
4: Han Z, Pantazis P, Lange TS, Wyche JH, Hendrickson EA. The staurosporine analog, Ro-31-8220, induces apoptosis independently of its ability to inhibit protein kinase C. Cell Death Differ. 2000 Jun;7(6):521-30. PubMed PMID: 10822275.
5: Zhou B, Zhang JP, Hu ZL, Tan YX, Qian DH. Ro 31-8220 inhibits release of interleukin-1 and interleukin-6 from mouse peritoneal macrophages induced by fibrin fibrinogen degradation products. Zhongguo Yao Li Xue Bao. 1999 May;20(5):449-51. PubMed PMID: 10678095.
6: Lingameneni R, Vysotskaya TN, Duch DS, Hemmings HC Jr. Inhibition of voltage-dependent sodium channels by Ro 31-8220, a 'specific' protein kinase C inhibitor. FEBS Lett. 2000 May 12;473(2):265-8. PubMed PMID: 10812087.
7: Kuz'mina TI, Denisenko VIu, Shapiev ISh. [Effect of the protein kinase C inhibitor Ro 31-8220 on Ca2+-responses, induced by somatotropin, in swine granulosa cells]. Tsitologiia. 1999;41(11):992-6. Russian. PubMed PMID: 10643054.
8: Hers I, TavarÃ© JM, Denton RM. The protein kinase C inhibitors bisindolylmaleimide I (GF 109203x) and IX (Ro 31-8220) are potent inhibitors of glycogen synthase kinase-3 activity. FEBS Lett. 1999 Nov 5;460(3):433-6. PubMed PMID: 10556511.
9: Zhou B, Zhang JP, Hu ZL, Tao XB, Qian DH. Effects of Ro 31-8220 on smooth muscle cell proliferation induced by fibrinogen degradation products. Zhongguo Yao Li Xue Bao. 1997 Sep;18(5):463-5. PubMed PMID: 10322943.
10: Standaert ML, Bandyopadhyay G, Antwi EK, Farese RV. RO 31-8220 activates c-Jun N-terminal kinase and glycogen synthase in rat adipocytes and L6 myotubes. Comparison to actions of insulin. Endocrinology. 1999 May;140(5):2145-51. PubMed PMID: 10218965.
11: Begemann M, Kashimawo SA, Lunn RM, Delohery T, Choi YJ, Kim S, Heitjan DF, Santella RM, Schiff PB, Bruce JN, Weinstein IB. Growth inhibition induced by Ro 31-8220 and calphostin C in human glioblastoma cell lines is associated with apoptosis and inhibition of CDC2 kinase. Anticancer Res. 1998 Sep-Oct;18(5A):3139-52. PubMed PMID: 9858877.
12: Barrett P, Davidson G, Hazlerigg DG, Morris MA, Ross AW, Morgan PJ. Mel 1a melatonin receptor expression is regulated by protein kinase C and an additional pathway addressed by the protein kinase C inhibitor Ro 31-8220 in ovine pars tuberalis cells. Endocrinology. 1998 Jan;139(1):163-71. PubMed PMID: 9421411.
13: Mahon TM, Matthews JS, O'Neill LA. Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1alpha in EL4 thymoma cells. Biochem J. 1997 Jul 1;325 ( Pt 1):39-45. PubMed PMID: 9224627; PubMed Central PMCID: PMC1218526.
14: Yeo EJ, Provost JJ, Exton JH. Dissociation of tyrosine phosphorylation and activation of phosphoinositide phospholipase C induced by the protein kinase C inhibitor Ro-31-8220 in Swiss 3T3 cells treated with platelet-derived growth factor. Biochim Biophys Acta. 1997 May 27;1356(3):308-20. PubMed PMID: 9194574.
15: Lin W, Zhang JP, Hu ZL, Feng ZH, Qian DH. Effects of Ro 31-8220 on lipopolysaccharides-induced hepatotoxicity and release of tumor necrosis factor from rat Kupffer cells. Zhongguo Yao Li Xue Bao. 1997 Jan;18(1):85-7. PubMed PMID: 10072903.
16: Heiskanen KM, Savolainen KM. Palmitic acid anilide-induced respiratory burst in human polymorphonuclear leukocytes is inhibited by a protein kinase C inhibitor, Ro 31-8220. Free Radic Biol Med. 1997;22(7):1175-82. PubMed PMID: 9098091.
17: Beltman J, McCormick F, Cook SJ. The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates Jun N-terminal kinase. J Biol Chem. 1996 Oct 25;271(43):27018-24. PubMed PMID: 8900190.
18: Harris TE, Persaud SJ, Jones PM. Atypical isoforms of pKc and insulin secretion from pancreatic beta-cells: evidence using GÃ¶ 6976 and Ro 31-8220 as Pkc inhibitors. Biochem Biophys Res Commun. 1996 Oct 23;227(3):672-6. PubMed PMID: 8885992.
19: Marley PD, Thomson KA. Inhibition of nicotinic responses of bovine adrenal chromaffin cells by the protein kinase C inhibitor, Ro 31-8220. Br J Pharmacol. 1996 Sep;119(2):416-22. PubMed PMID: 8886429; PubMed Central PMCID: PMC1915873.
20: Geiselhart L, Conti DJ, Freed BM. RO 31-8220, a novel protein kinase C inhibitor, inhibits early and late T cell activation events. Transplantation. 1996 Jun 15;61(11):1637-42. PubMed PMID: 8669110.
125314-64-9 (free base).