Name: ON123300
Brand: Selleck Chemicals
SKU: S8161
Rating: 5 (4 reviews)

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.96%

99.96

Relaterade mål	HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase Casein Kinase
Övrigt CDK Inhibitorer	AS2863619 Ro-3306 SEL120 (SEL120-34A) hydrochloride INX-315 Tagtociclib (PF-07104091) PF-07220060 (CDK4/6-IN-6) AZD4573 Enitociclib (BAY 1251152) Samuraciclib (ICEC0942) hydrochloride Dinaciclib (SCH 727965)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	429.52	Formel	C₂₄H₂₇N₇O	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	1357470-29-1	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel
Synonymer	N/A			Smiles	CN1CCN(CC1)C2=CC=C(C=C2)NC3=NC=C4C=C(C(=O)N(C4=N3)C5CCCC5)C#N

Löslighet (Solubility)

In vitro
Batch:

DMSO : 29 mg/mL (67.51 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	0.550mg/ml (1.28mM)	Taking the 1 mL working solution as an example, add 50 μL of 11 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	0.250mg/ml (0.58mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC₅₀/Ki	CDK4/CyclinD1 (Cell-free assay) 3.87 nM ARK5 (Cell-free assay) 4.95 nM RET (Cell-free assay) 9.2 nM CDK6/CyclinD1 (Cell-free assay) 9.82 nM Fyn (Cell-free assay) 11 nM PDGFRβ (Cell-free assay) 26 nM FGFR1 (Cell-free assay) 26 nM PI3Kδ (Cell-free assay) 144 nM FGFR1 (Cell-free assay) 260 nM
In vitro	ON123300 inhibits U87 glioma cell proliferation with an IC50 3.4±0.1 μmol/L and reduces phosphorylation of Akt, yet it also unexpectedly induces Erk activation, both in a dose- and time-dependent manner that subsequently is attributed to relieving Akt mediated C-Raf S259 inactivation and activating a p70S6K-initiated PI3K-negative feedback loop. This compound also inhibits CDK4/6 and PI3K-δ and exhibits potent activity against mantle cell lymphomas (MCLs). It is a potent inhibitor of CDK4, with an IC50 of 3.8 nM, with little inhibitory activity against CDKs 1,2,5 and 8. MCL cell lines treated with this chemical accumulate in the G1 phase at lower concentrations (0.1-1.0μM), at higher concentrations of the compound, a large proportion of the cells progress through the S and G2/M phases of the cell cycle and eventually accumulate in the sub-G1 phase, suggesting an induction of apoptosis. It also inhibits the phosphorylation of pRb and p130 in a dose-dependent manner. This treatment results in inhibition of FOXO1 phosphorylation, a target of mTOR.
In vivo	In a preclinical brain tumor model (U87MG), ON123300 shows high brain and brain tumor accumulation. Consistent with the in vitro studies, single agent this compound causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors. It is highly bound (99.4%) to plasma proteins in mice and rapidly penetrates into brain. It has proficient BBB penetration and accumulates in normal brain. The pharmacokinetic profiles of plasma this chemical concentration are multiexponential and overall declines fairly rapidly with terminal elimination half-lives of 1.5 hours. Mouse xenograft assays show a strong inhibition of MCL tumor growth in this compound-treated animals. Safety studies in mice suggest that it is orally bio-available and is minimally toxic when administered orally or intraperitoneally.
Referenser	[1] https://pubmed.ncbi.nlm.nih.gov/24568969/ [2] https://pubmed.ncbi.nlm.nih.gov/23180160/ [3] https://pubmed.ncbi.nlm.nih.gov/26174628/

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer	Rekrytering	Tillstånd	Sponsor/Samarbetspartners	Startdatum	Faser
NCT06351644	Not yet recruiting	Relapsed and/or Refractory Multiple Myeloma	Adriana Rossi\|Icahn School of Medicine at Mount Sinai	June 3 2024	Phase 1\|Phase 2
NCT04739293	Recruiting	Solid Tumors Adult	Traws Pharma Inc.	May 13 2021	Phase 1

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C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

ON123300 CDK Hämmare

Molekylvikt: 429.52