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CAS No. :	55837-20-2
Formula :	C₁₆H₁₇BrClN₃O₃
M.W :	414.68
SMILES Code :	O=C1N(CC(C[C@H]2NCCC[C@@H]2O)=O)C=NC3=C1C=C(Cl)C(Br)=C3
Synonyms :	RU-19110
MDL No. :	MFCD09834143

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Calu-3 cells	3 µM		marked resistance to SARS-CoV-2 infection	Nat Commun. 2021 Jun 23;12(1):3907.
Caco-2 cells	3 µM	18 h	marked reduction in endogenous TMPRSS2 protein expression	Nat Commun. 2021 Jun 23;12(1):3907.
Beas-2B cells	10 µM	18 h	reduce TMPRSS2-HiBiT abundance	Nat Commun. 2021 Jun 23;12(1):3907.
murine T cells	3.6 ± 0.4 nM	24 h	Selectively inhibited TH17 cell differentiation without affecting TH1, TH2, or iTreg cell differentiation	Science. 2009 Jun 5;324(5932):1334-8.
WM852, 501mel and 888mel human melanoma cell lines	200nM	24 h	Halofuginone significantly inhibited TGF-β-induced activity of the (CAGA)9 promoter in all the melanoma lines analyzed.	Cancer Res. 2012 Dec 1;72(23):6247-56.
Human 1205Lu melanoma cells	50-300nM	24, 48 and 72 h	Halofuginone 200 and 300nM treatments for 48 and 72 h significantly induced cell death.	Cancer Res. 2012 Dec 1;72(23):6247-56.
Human 1205Lu melanoma cells	200nM	4 h	Halofuginone pretreatment for 4 h followed by TGF-β treatment for 15 to 60 min significantly increased expression of Smad7 mRNA.	Cancer Res. 2012 Dec 1;72(23):6247-56.
Human 1205Lu melanoma cells	200nM	4 and 12 h	Halofuginone pretreatment for 4 and 12 h followed by 30 mins of TGF-β treatment decreased the levels of phosphoSmad2 and phosphoSmad3 levels, while total Smad2/3 levels remained unchanged.	Cancer Res. 2012 Dec 1;72(23):6247-56.
Human 1205Lu melanoma cells	50-300nM	24 h	Halofuginone dose-dependently inhibited TGF-β-induced promoter activity.	Cancer Res. 2012 Dec 1;72(23):6247-56.
HUVEC cells	50, 100 or 200 ng/mL	24 h	To evaluate the effect of HF on gene expression in endothelial cells, results showed that HF increased VEGF gene expression and protein secretion, but had no significant effect on the gene expression of ANGPT-1, HIF-1α, TIMP2 and CXCL10, while ANGPT-2 expression was increased.	J Exp Clin Cancer Res. 2015 Jun 23;34(1):65.
NB4 cells	50, 100 or 200 ng/mL	6 h	To evaluate the effect of HF on gene expression in leukemic cells, results showed that HF down-regulated the expression of several pro-angiogenic factors, including HIF-1α, HGF, ANGPT-1 and ANGPT-2, while up-regulating the anti-angiogenic factors TIMP2 and CXCL10.	J Exp Clin Cancer Res. 2015 Jun 23;34(1):65.
human pancreatic stellate cells	50 nM and 100 nM	48 h	inhibition of α-SMA expression, reduction of fibrosis-related genes (e.g., type-I collagen and hyaluronan synthase-2), and inhibition of cell proliferation	Cancer Res. 2019 Jan 15;79(2):372-386.
murine pancreatic stellate cells	50 nM and 100 nM	48 h	inhibition of α-SMA expression, reduction of fibrosis-related genes (e.g., type-I collagen and hyaluronan synthase-2), and inhibition of cell proliferation	Cancer Res. 2019 Jan 15;79(2):372-386.
293T cells	50 nM	24 h	Halofuginone treatment significantly decreased the expression of NRF2-Δ100aa and NRF2-C but had no obvious effect on NRF2-N expression.	Redox Biol. 2022 Feb;49:102224.
NCTC 1469 cells	0–200 nM	24 h	Halofuginone treatment decreased the expression of NRF2, HO-1, and NQO-1.	Redox Biol. 2022 Feb;49:102224.
HepG2 cells	0–200 nM	24 h	Halofuginone treatment decreased the expression of NRF2, HO-1, and NQO-1, and this reduction was achieved via the proteasome pathway.	Redox Biol. 2022 Feb;49:102224.
breast cancer MCF-7 cells	100 nM	4, 8, 24 h	Induced both the AAR and the autophagy pathways time-dependently	Cell Commun Signal. 2019 May 2;17(1):39.
ovarian cancer OAW-42 cells	100 nM	4, 8, 24 h	Induced both the AAR and the autophagy pathways time-dependently	Cell Commun Signal. 2019 May 2;17(1):39.
thyroid cancer WRO cells	100 nM	4, 8, 24 h	Induced both the AAR and the autophagy pathways time-dependently	Cell Commun Signal. 2019 May 2;17(1):39.
SW480 cells	20 nM	2 h	Inhibits autophagy under nutrient-poor condition	Cell Death Dis. 2017 May 11;8(5):e2789.
HCT116 cells	20 nM	2 h	Inhibits autophagy under nutrient-poor condition	Cell Death Dis. 2017 May 11;8(5):e2789.
SW480 cells	20 nM	12 h	Induces autophagy under nutrient-rich condition	Cell Death Dis. 2017 May 11;8(5):e2789.
HCT116 cells	20 nM	12 h	Induces autophagy under nutrient-rich condition	Cell Death Dis. 2017 May 11;8(5):e2789.

C57BL/6J mice and Lewis rats	Anterior cruciate ligament transection (ACLT) models	Intraperitoneal injection	1 mg/kg	Injected every other day for 1 month	Halofuginone attenuates OA progression by inhibition of Th17-induced osteoclastogenesis, TGF-β-dependent Smad2/3 phosphorylation and angiogenesis	Ann Rheum Dis. 2016 Sep;75(9):1714-21
Nude mice	1205Lu melanoma bone metastasis model	Intraperitoneal (i.p.) injection	1 or 5µg/mouse	Daily until the end of the experiment	Preventive treatment with halofuginone significantly reduced osteolytic lesion area.	Cancer Res. 2012 Dec 1;72(23):6247-56.
NOD/SCID mice	Acute Promyelocytic Leukemia transplanted model	Intraperitoneal injection	150 μg/kg	Daily for 21 days	To evaluate the antileukemic effects of HF in vivo, results showed that HF treatment significantly reduced WBC counts, decreased accumulation of immature cells in the BM and spleen, and reduced the number of VEGF+ cells and VEGF gene expression.	J Exp Clin Cancer Res. 2015 Jun 23;34(1):65.
Mice	KrasG12D/+;p53R172H/+;Pdx-1-Cre (KPC) genetically engineered mouse model	Intraperitoneal injection	0.75 mg/kg	3 times/week, total of 5 doses	Reduced tumor volume growth, increased necrotic areas, improved drug distribution, and promoted anti-tumor immune cell infiltration	Cancer Res. 2019 Jan 15;79(2):372-386.
C57BL/6 mice	Regular chow-fed mice	Intraperitoneal injection	3 mg/kg	3 days	Halofuginone treatment decreased the protein expression of NRF2, HO-1, and NQO-1 in the liver.	Redox Biol. 2022 Feb;49:102224.
BALB/c nude mice	HCT116 xenograft model	Intraperitoneal injection	0.1 mg/kg	Once daily for 2 weeks	Retards tumor growth under both standard chow diet and caloric restriction conditions	Cell Death Dis. 2017 May 11;8(5):e2789.

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CAS No.: 55837-20-2

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CAS No.: 55837-20-2

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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