ABOUT THE PROJECT
IBH-1
— An allosteric negative modulator of nicotinic receptor type α7 was derived from the human skin protein SLURP-1, which protects epithelial cells from oncogenic transformation.
С потреблением табака связано развитие различных карцином (легкого, шеи, желудка, поджелудочной железы, желчного пузыря, печени, толстой кишки, груди, шейки матки, мочевого пузыря и почек). Молекулярный механизм развития и прогрессирования рака, вызванного табаком, - прямая активация никотиновых ацетилхолиновых рецепторов α7 типа (α7-nAChR) агонистом никотина и его нитрозаминовыми производными, присутствующими в табачном дыме. Активация α7-nAChR в свою очередь стимулирует митогенные, антиапоптотические и пролиферативные внутриклеточные сигнальные пути и передачу сигналов через рецепторы EGF и VEGF, а также β-адренорецепторы. Отрицательная модуляция nAChR считается перспективным компонентом противоопухолевой терапии.
An allosteric negative modulator of nicotinic receptor type α7 was derived from the human skin protein SLURP-1, which protects epithelial cells from oncogenic transformation.
It was shown, that the recombinant modulator can effectively suppress the growth of skin, lung, breast, and intestinal carcinoma cells. Effective modulator concentrations are in the range between 1-10 nM. At the same time, on normal skin cells the drug starts acting at concentrations exceeding 100 nM.
Immunogenicity study of the drug on animal model showed, that the drug does not cause an immune response when administered every day.
Preclinical testing of the product is currently underway (the preclinical stage is 10% complete).
Russian patent application for joint use of the drug prototype with classical chemotherapeutic agents has been filed. The other Russian patent application is being prepared for the structure and method of obtaining the active substance.
The full cycle of clinical trials are planned to be completed in 2027.
Мы разработали синтетический пептид, который воспроизводит активность полноразмерного белка SLURP-1 in vitro и в терапевтических дозах не действует на здоровые клетки. Рекомбинантный полипептид, избирательно действующий на α7-nAChR, — это первый в своем классе таргетный препарат для лечения агрессивных солидных опухолей эпителиального происхождения.
ИБХ-1 предназначен для замены классической химиотерапии, обладающей высокой системной токсичностью. Препарат разработан на основе природного белка человека, который защищает эпителиальные клетки от онкогенной трансформации. Активен против агрессивных метастатических злокачественных опухолей легких, толстой кишки, кожи и груди, в том числе вызванных употреблением никотина. Возможна комбинация ИБХ-1 с классическими химиотерапевтическими препаратами, что значительно снижает дозу токсической химиотерапии.
Description
& EFFECT
Lyophilisate in sterile ampoules for injection.
Can be used in therapy of aggressive solid tumors of epithelial origin, the modulator acts on nicotinic receptors of a7 type, suppresses cell growth in carcinomas of the skin, lung, breast and intestinum. In co-application it enhances the effect of antitumor drugs from the classes of HER2 receptor inhibitors (gefitinib), cytostatics (doxorubicin), proteasome inhibitors (bortezomib).
This product is indicated for the combined therapy of skin, lung, colon, breast and other types of tumors of epithelial origin.
EFFECT
- Stops the cancer cells growth
- Reduces metastasis
- Causes secretion of endogenous SLURP-1 by epithelial cells
- Prevents nicotine-stimulated lung carcinoma cell proliferation and suppresses α7-nAChR expression
DESCRIPTION
& EFFECT
Lyophilisate in sterile ampoules for injection.
Can be used in therapy of aggressive solid tumors of epithelial origin, the modulator acts on nicotinic receptors of a7 type, suppresses cell growth in carcinomas of the skin, lung, breast and intestinum. In co-application it enhances the effect of antitumor drugs from the classes of HER2 receptor inhibitors (gefitinib), cytostatics (doxorubicin), proteasome inhibitors (bortezomib).
This product is indicated for the combined therapy of skin, lung, colon, breast and other types of tumors of epithelial origin.
EFFECT
- Stops the cancer cells growth
- Reduces metastasis
- Causes secretion of endogenous SLURP-1 by epithelial cells
- Prevents nicotine-stimulated lung carcinoma cell proliferation and suppresses α7-nAChR expression
DESCRIPTION
& EFFECT
Lyophilisate in sterile ampoules for injection.
Can be used in therapy of aggressive solid tumors of epithelial origin, the modulator acts on nicotinic receptors of a7 type, suppresses cell growth in carcinomas of the skin, lung, breast and intestinum. In co-application it enhances the effect of antitumor drugs from the classes of HER2 receptor inhibitors (gefitinib), cytostatics (doxorubicin), proteasome inhibitors (bortezomib).
This product is indicated for the combined therapy of skin, lung, colon, breast and other types of tumors of epithelial origin.
EFFECT
- Stops the cancer cells growth
- Reduces metastasis
- Causes secretion of endogenous SLURP-1 by epithelial cells
- Prevents nicotine-stimulated lung carcinoma cell proliferation and suppresses α7-nAChR expression
BENEFITS
ПОВЫШЕННАЯ
ФАРМАКОКИНЕТИКА
ИММУНОГЕННОСТЬ
ТОКСИЧНОСТЬ
DEVELOPERS
The Shemyakin & Ovchinnikov Institute of bioorganic chemistry (IBCh) of the Russian Academy of Sciences is one of the largest Russian scientific organizations. The Institute is a leader in fundamental and innovative researches on the fields of molecular, structural and cell biology, bioorganic chemistry, biophysics, bioengineering, cell technologies, “in vivo” molecular based bioimaging, genome editing, bioinformatics etc. This multidisciplinary structure allows large-scale research at the interface of sciences, where the most interesting scientific discoveries are born today.
The hallmark of the IBCh RAS is the concentration of efforts and resources on solving the most urgent and complicated problems on the field of life sciences. Talented young people and leading specialists, including Russian and foreign science leaders, Nobel Prize laureates and members of the international advisory council of the Institute are involved in.
Ekaterina Lyukmanova
Zakhar Shenkarev
Mikhail Shulepko
Maksim Bychkov
PUBLICATIONS
8:47 Snakes Will Help Man Fight Cancer. More precisely - scientists specializing in the poisons of these reptiles.
Biochemical basis of skin disease Mal de Meleda: SLURP-1 mutants differently affect keratinocyte proliferation and apoptosis.
M.A. Shulepko, M.L. Bychkov, Z.O. Shenkarev, D.S. Kulbatskii, A.M. Makhonin, A.S. Paramonov, A.O. Chugunov, M.P. Kirpichnikov, E.N. Lyukmanova.
Jpurnal of Investigative Dermatology, 2021. In print.
Paramonov AS, Kocharovskaya MV, Tsarev AV, Kulbatskii DS, Loktyushov EV, Shulepko MA, Kirpichnikov MP, Lyukmanova EN, Shenkarev ZO.
Int J Mol Sci. 2020, 21(19):7280. doi: 10.3390/ijms21197280.
Shulepko MA, Bychkov ML, Lyukmanova EN, Kirpichnikov MP.
Dokl Biochem Biophys. 2020, 493(1):211-214. doi: 10.1134/S1607672920040134.
Shulepko MA, Bychkov ML, Shlepova OV, Shenkarev ZO, Kirpichnikov MP, Lyukmanova EN.
Int Immunopharmacol. 2020; 82:106303.
Bychkov M.L., Shulepko M.A., Shlepova O.V., Lyukmanova E.N., Kirpichnikov M.P.
Reports of the Academy of Sciences, Vol. 489, No. 5 (2019), pp. 517-520
Lyukmanova EN, Bychkov ML, Sharonov GV, Efremenko AV, Shulepko MA, Kulbatskii DS, Shenkarev ZO, Feofanov AV, Dolgikh DA, Kirpichnikov MP.
Br J Pharmacol. (2018) 175(11):1973-1986. doi: 10.1111/bph.14194.
Lyukmanova EN, Shulepko MA, Kudryavtsev D, Bychkov ML, Kulbatskii DS, Kasheverov IE, Astapova MV, Feofanov AV, Thomsen MS, Mikkelsen JD, Shenkarev ZO, Tsetlin VI, Dolgikh DA, Kirpichnikov MP.
PLoS One. 2016 ; 11(2):e0149733. doi: 10.1371/journal.pone.0149733.
Е. N. Lyukmanova, M. A. Shulepko, M. L. Bychkov, Z. O. Shenkarev, A. S. Paramonov, A. O. Chugunov, A. S. Arseniev, D. A. Dolgikh, M. P. Kirpichnikov.
(2014), Acta Naturae, 6(4): 58-65.
Human SLURP-1 neuromodulator: bacterial production, interaction with the muscle nicotinic acetylcholine receptor, structure and conformational heterogeneity in solution.
M.A. Shulepko, E.N. Lyukmanova, A.S. Paramonov, A.A. Lobas, Z.O. Shenkarev, I.E. Kasheverov, V.I. Tsetlin, D.A. Dolgikh, A.S. Arseniev, M.P. Kirpichnikov.
(2013) Biochemistry, Vol. 78(2): 276-285.
CONTACT us
get in touch
Sergey Semenov