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CAS No. :	1672662-14-4
Formula :	C₁₇H₁₀F₅NO₄S
M.W :	419.32
SMILES Code :	O[C@@H]1C(F)(F)CC2=C(OC3=CC(C#N)=CC(F)=C3)C=CC(S(=O)(C(F)F)=O)=C12
MDL No. :	MFCD32062659

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319
Precautionary Statements:	P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

UMRC2	2 µM	2 to 5 weeks	Evaluate the effect of PT2399 on the growth of UMRC2 cells in soft agar, results showed PT2399 did not significantly suppress the growth of UMRC2 cells.	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119
CAKI2	2 µM	2 to 5 weeks	Evaluate the effect of PT2399 on the growth of CAKI2 cells in soft agar, results showed PT2399 did not significantly suppress the growth of CAKI2 cells.	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119
769-P	2 µM	2 to 5 weeks	Evaluate the effect of PT2399 on the growth of 769-P cells in soft agar, results showed PT2399 did not significantly suppress the growth of 769-P cells.	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119
OSRC2	2 µM	2 to 5 weeks	Evaluate the effect of PT2399 on the growth of OSRC2 cells in soft agar, results showed PT2399 suppressed the growth of OSRC2 cells.	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119
786-O	2 µM	2 to 5 weeks	Evaluate the effect of PT2399 on the growth of 786-O cells in soft agar, results showed PT2399 suppressed the growth of 786-O cells.	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119
C4-2 cells	50 µM	24 hours	PT2399 significantly decreased HSD3B1 expression in HR cells and inhibited nuclear localization of HIF2α and its binding to ARNT.	Cancer Res. 2022 Jul 5;82(13):2417-2430
LNCaP cells	50 µM	24 hours	PT2399 significantly decreased HSD3B1 expression in HR cells and inhibited nuclear localization of HIF2α and its binding to ARNT.	Cancer Res. 2022 Jul 5;82(13):2417-2430
769-P cells	2 µM	48 hours	PT2399 failed to down-regulate cyclin D1 abundance in 769-P cells.	Sci Signal. 2019 Oct 1;12(601):eaay0482
UMRC-2 cells	2 µM	48 hours	PT2399 failed to down-regulate cyclin D1 abundance in UMRC-2 cells.	Sci Signal. 2019 Oct 1;12(601):eaay0482
A498 cells	2 µM	48 hours	PT2399 had variable effects on basal cyclin D1 mRNA and protein abundance in the A498 cells.	Sci Signal. 2019 Oct 1;12(601):eaay0482
786-O cells	2 µM	48 hours	PT2399 monotherapy did not cause a statistically significant increase in the VHL-Tdtomato:EV-GFP ratio, consistent with earlier studies showing that 786-O cells tolerate the loss of HIF-2 α in short-term cultures under high serum conditions.	Sci Signal. 2019 Oct 1;12(601):eaay0482

Mice	Renal cell carcinoma tumorgraft model	Oral gavage	100 mg/kg	Every 12 hours for approximately 28 days	To evaluate the antitumor effects of PT2399 in a renal cell carcinoma tumorgraft model. Results showed PT2399 suppressed tumorigenesis in 56% of the lines and was more active than sunitinib.	Nature. 2016 Nov 3;539(7627):112-117
Nude mice	786-O cell orthotopic xenografts	Oral gavage	20 mg/kg	Daily for 28 days	PT2399 monotherapy, as expected, suppressed 786-O cell tumor growth, with a trend toward greater suppression with the combination with palbociclib.	Sci Signal. 2019 Oct 1;12(601):eaay0482
Mice	Adenomyosis mouse model	Oral gavage	30 mg/kg	Twice daily for 2 days	Inhibited HIF-2α expression and increased Hoxa10 and Hoxa11 expression	Reprod Biol Endocrinol. 2021 Jan 8;19(1):7
Mice	Epas1S305M/S305M knock-in mice	Oral gavage	30 mg/kg	Twice daily for 8 weeks	PT2399 suppressed HIF-2α target gene expression in wild-type mice, ameliorated high-fat diet-induced obesity and metabolic dysfunction, but had no effect in mutant mice.	Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):13240-13245
Female Ncr nude mice	786-O-Fluc cell orthotopic xenograft model	Oral gavage	30 mg/kg	Once daily for 28 days	Evaluate the effect of PT2399 on the growth of 786-O-Fluc cell xenografts, results showed PT2399 significantly inhibited tumor growth and reduced Cyclin D1 and Ki67 expression.	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119
Mice (C57Bl/6J background)	Wild-type mice and HIF-2α conditional knockout mice	Oral gavage	50 mg/kg	Twice daily for 5 consecutive days followed by a 2-day washout period, total 14 days	PT2399 treatment ameliorated radiation-induced bone loss but resulted in reduced red blood cell (RBC) counts and hemoglobin (HGB) amounts, indicating an anemic side effect.	Sci Transl Med. 2023 Nov 29;15(724):eabo5217
C57BL/6 mice	Subcutaneous and orthotopic pancreatic cancer models with KPC cells	Oral gavage	50 mg/kg	5 days per week, twice daily, for 2-3 weeks	To evaluate the therapeutic effect of PT2399 combined with immune checkpoint blockade on pancreatic cancer. Results showed that PT2399 combined with αCTLA4 significantly slowed tumor growth and improved survival.	Gastroenterology. 2022 Jun;162(7):2018-2031
Mice	Vhl/Trp53/Rb1 mutant mouse model	Oral gavage	50 mg/kg	Twice daily for 14 days	Evaluating the therapeutic effects of PT2399 in a HIF-2α inhibitor-resistant mouse ccRCC model, showing no significant effect on tumor growth	Cancers (Basel). 2021 Sep 25;13(19):4801
Mice	786-O and OSRC2 orthotopic xenografts	Oral gavage	30 mg/kg	Daily for 28 days	Assess the suppression of tumor growth by PT2399	Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2120403119

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CAS No.: 1672662-14-4

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CAS No.: 1672662-14-4

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Precautionary Statements-General

Prevention

Response

Storage

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Physical hazards

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Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	2.38mL 0.48mL 0.24mL	11.92mL 2.38mL 1.19mL	23.85mL 4.77mL 2.38mL
Dissolving Methods	Animal experiment Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn: in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day; The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound. Protocol 1 Protocol 2

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