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CAS No. :	1393-48-2
Formula :	C₇₂H₈₅N₁₉O₁₈S₅
M.W :	1664.89
SMILES Code :	O=C(N[C@@]1(CCC(C2=NC(C(NC(C(NC(C(N)=O)=C)=O)=C)=O)=CS2)=N[C@H]1C3=CSC([C@@H](NC(C4=CSC([C@@H](NC5=O)C(O)([C@@H](C)O)C)=N4)=O)[C@H](OC(C6=NC7=C(C([C@H](C)O)=C6)C=C[C@@H](N[C@H]8C(CC)C)[C@@H]7O)=O)C)=N3)C9=NC(C(N[C@H](C(N/C(C%10=N[C@@H]5CS%10)=C/C)=O)[C@@H](C)O)=O)=CS9)[C@@H](NC(C(NC([C@@H](NC8=O)C)=O)=C)=O)C
Synonyms :	Bryamycin; Thiactin; Thiostreptin A
MDL No. :	MFCD00135828

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H312-H332
Precautionary Statements:	P280

E. coli 70S ribosomes	0.15 µM	10 minutes	To study the inhibitory effect of Thiostrepton on the GTPase activity of EF-G and EF4, the results showed that Thiostrepton significantly inhibited the GTPase activity of both EF-G and EF4.	Nucleic Acids Res. 2012 Jan;40(1):360-70.
EL4 cells	0.5 µM, 1 µM, 2 µM	24 hours	To investigate the effect of TST on RORγt expression in EL4 cells, results showed that TST induced ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt.	Cell Mol Immunol. 2023 Nov;20(11):1352-1366.
Human monocyte-derived macrophages (hMDMs)	2.5 µM	24 hours	Thiostrepton induced hMDMs to express proinflammatory cytokines TNFα and IL-1β and downregulate the M2 chemokine CCL24. Functional enrichment analysis showed that IFN/NFκB pathway, TNF-mediated pathway, oxidative-reduction process, protein polyubiquitination, and cellular response to LPS were upregulated, while DNA replication, cell cycle, and cell matrix adhesion were downregulated.	Nat Commun. 2021 Feb 3;12(1):773.
Mouse bone marrow macrophages (BMMs)	2.5 µM	24 hours	Thiostrepton inhibited the expression of TAM/M2-associated genes Arg1, Fizz1, Vegfa, Ym1, and Tgfb but upregulated the expression of M1-associated genes Tnf, Il1b, Cxcl2, and Nos2.	Nat Commun. 2021 Feb 3;12(1):773.
Human peripheral blood mononuclear cell (PBMC)-derived macrophages	10 mM	24 hours	To study the effect of Thiostrepton on macrophage polarization, results showed that Thiostrepton did not significantly promote M2 to M1 macrophage repolarization but caused slight reductions in CD86 and CD206 expression in M2 macrophages.	Haematologica. 2024 Feb 1;109(2):639-645.
70S ribosomes	100 µM	3 minutes	To study the effect of thiostrepton on EF-G-dependent GTP hydrolysis, results showed that thiostrepton inhibited the turnover of EF-G but did not affect single-round GTP hydrolysis.	Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9586-90.
H1299 cells	5 µM	48 hours	Reduced FOXM1 and PD-L1 expression, inhibited cell proliferation	Adv Sci (Weinh). 2022 Oct;9(29):e2202702.
PC9 cells	5 µM	48 hours	Reduced FOXM1 and PD-L1 expression, inhibited cell proliferation	Adv Sci (Weinh). 2022 Oct;9(29):e2202702.
HCT-8 cells	2 µM	48 hours	To test the anti-proliferative activity of Thiostrepton against CRC cells	J Exp Clin Cancer Res. 2020 Jan 28;39(1):23.
HCT116 cells	2 µM	48 hours	To test the anti-proliferative activity of Thiostrepton against CRC cells	J Exp Clin Cancer Res. 2020 Jan 28;39(1):23.
HCT-15 cells	5 µM and 10 µM	48 hours	Induced apoptosis in CRSC subpopulations and inhibited their sphere and colony formation capabilities.	Cell Death Dis. 2015 Jul 2;6(7):e1801.
HT-29 cells	5 µM and 10 µM	48 hours	Induced apoptosis in CRSC subpopulations and inhibited their sphere and colony formation capabilities.	Cell Death Dis. 2015 Jul 2;6(7):e1801.
Panc-1	0–250 µM	48 hours	To evaluate the inhibitory effect of TST on the proliferation of pancreatic cancer cells, the results showed that TST significantly reduced the growth of pancreatic cancer cells in a dose-dependent manner.	Cell Death Dis. 2022 Jul 20;13(7):630.
MIA PaCa-2	0–250 µM	48 hours	To evaluate the inhibitory effect of TST on the proliferation of pancreatic cancer cells, the results showed that TST significantly reduced the growth of pancreatic cancer cells in a dose-dependent manner.	Cell Death Dis. 2022 Jul 20;13(7):630.
BxPC-3	0–250 µM	48 hours	To evaluate the inhibitory effect of TST on the proliferation of pancreatic cancer cells, the results showed that TST significantly reduced the growth of pancreatic cancer cells in a dose-dependent manner.	Cell Death Dis. 2022 Jul 20;13(7):630.
HTERT-HPNE	0–250 µM	48 hours	To evaluate the inhibitory effect of TST on the proliferation of normal pancreatic ductal epithelial cells, the results showed that TST had low toxicity to normal cells.	Cell Death Dis. 2022 Jul 20;13(7):630.
Human neuroglioma H4 cells	0.5, 5, 50 µM	6 hours	Autophagy induction was assessed by measuring GFP-LC3 positive puncta, and 175 compounds were selected	J Immunother Cancer. 2020 Mar;8(1):e000462.
Human osteosarcoma U2OS cells	50 µM	6 hours	ATP release was assessed by measuring quinacrine positive dots, and Thiostrepton was identified as a potential ICD enhancer	J Immunother Cancer. 2020 Mar;8(1):e000462.
Th17 cells	0.01 µM, 0.25 µM, 5 µM	72 hours	To investigate the effect of TST on Th17 cell differentiation, results showed that TST significantly inhibited Th17 cell differentiation and reduced IL-17A production and RORγt expression.	Cell Mol Immunol. 2023 Nov;20(11):1352-1366.
Acute myeloid leukemia (AML) cell lines	1.91 mM to 38.67 mM (ED50)	72 hours	To study the cytotoxicity of Thiostrepton on leukemic cells, results showed that Thiostrepton exhibited significant cytotoxicity against AML cell lines with ED50 values ranging from 1.91 mM to 38.67 mM.	Haematologica. 2024 Feb 1;109(2):639-645.
Yeast strain 6EA1	100 µM		To test the inhibitory effect of Thiostrepton on yeast strain 6EA1 expressing bacterial protein L11, results showed that the strain was sensitive to Thiostrepton with an IC50 of approximately 100 µM.	Nucleic Acids Res. 2007;35(21):7109-17.
Pulmonary fibroblasts	10 µM		Inhibition of FOXM1 expression significantly reduced the expression of α-SMA and COL1A1 and impaired the migration ability of pulmonary fibroblasts.	Stem Cell Res Ther. 2024 Sep 18;15(1):309.

Mice	B16F10 melanoma model	Intraperitoneal or subcutaneous injection	150 or 300 mg/kg (intraperitoneal injection), 20 mg/kg (subcutaneous injection)	Administered on day 6 and day 12	Thiostrepton significantly suppressed tumor growth and showed additive effects with TA99. Flow cytometry analysis revealed elevated levels of macrophages and monocytes in tumors from mice treated with thiostrepton or thiostrepton plus TA99, with upregulated expression of iNOS and CD86 and downregulated expression of Arg1 in TAMs.	Nat Commun. 2021 Feb 3;12(1):773.
BALB/c Nude mice	H1299 and PC9 xenograft model	Intraperitoneal injection	17 mg/kg	Every 2 days for 9 days	Significantly downregulated PD-L1 expression and reduced tumor volume	Adv Sci (Weinh). 2022 Oct;9(29):e2202702.
BALB/c Nude mice	Subcutaneous tumour model	Intraperitoneal injection	17 mg/kg	Three times a week for 3 weeks	To evaluate the inhibitory effect of TST on the growth of subcutaneous tumours, the results showed that TST significantly inhibited tumour growth, and Fer-1 reversed this effect.	Cell Death Dis. 2022 Jul 20;13(7):630.
Mice	DSS-induced colitis model	Intraperitoneal injection	20 mg/kg	Every other day, for 7 days	To investigate the therapeutic effect of TST on DSS-induced colitis, results showed that TST significantly alleviated colitis symptoms and controlled colonic inflammation by modulating dysbiosis.	Cell Mol Immunol. 2023 Nov;20(11):1352-1366.
C57BL/6 mice	MCA205 or TC-1 tumor model	Intraperitoneal injection	200 mg/kg	Once daily 1 day before, on, and 1 day after chemotherapy, then 40 mg/kg three times per week	Thiostrepton enhanced the anticancer activity of oxaliplatin, further diminishing tumor size and extending the survival of the animals	J Immunother Cancer. 2020 Mar;8(1):e000462.
Mice	BLM-induced pulmonary fibrosis models	Intraperitoneal injection	30 mg/kg	Every other day for 2 weeks	Inhibition of FOXM1 expression significantly reduced pulmonary fibrosis, decreased collagen deposition, and lowered the expression of fibrotic markers such as α-SMA and COL1A1.	Stem Cell Res Ther. 2024 Sep 18;15(1):309.
Nude mice	CRC xenograft model	Intraperitoneal injection	500 mg/kg/day	Every three days for 21 days	To evaluate the anti-tumor effect of Thiostrepton on CRC xenograft model	J Exp Clin Cancer Res. 2020 Jan 28;39(1):23.

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CAS No.: 1393-48-2

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CAS No.: 1393-48-2

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed