SR-3029 is a strong inhibitor of CK1δ/CK1ε, with IC50 values of 44 nM and 260 nM, respectively. It competes with ATP, having Kis of 97 nM for CK1δ/CK1ε. SR-3029 also inhibits CDK6/cyclin D3, CDK6/cyclin D1, CDK4/cyclin D3, CDK4/cyclin D1, and FLT3, with IC50s of 427, 428, 368, 576, and 3000 nM, respectively. It exhibits inhibitory activity on A375 cells, with an EC50 of 86 nM[1]. SR-3029's efficacy is lower against MCF7 and T47D breast cancer cells, as well as the MCF10A cell line, all of which have low CK1δ expression[2].
SR-3029 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MDA-MB-231
5-70 nM
72 hours
Inhibited cell proliferation and induced apoptosis
Sci Transl Med. 2015 Dec 16;7(318):318ra202.
UM-UC-3
5-400 nM
72 hours
Inhibition of cell proliferation
Mol Cancer Ther. 2020 Aug;19(8):1623-1635.
MIAPaCa-2
5-400 nM
72 hours
Inhibition of cell proliferation
Mol Cancer Ther. 2020 Aug;19(8):1623-1635.
HCT116 cells
100 nM
24 hours
To evaluate the effect of SR3029 on AES protein level, results showed that SR3029 treatment increased AES protein expression.
Theranostics. 2021 Mar 4;11(9):4421-4435.
HEK293T cells
0.2 μM
12 hours
SR3029 increased the protein level of Axin1 and attenuated the RSPO1-induced degradation of Axin1 protein.
Cell Commun Signal. 2024 Jan 5;22(1):14.
HCT116 cells
240 nM
24 hours
To study the inhibitory effect of SR-3029 on β-catenin acetylation
Front Oncol. 2022 Apr 12;12:844477.
SW480 cells
240 nM
24 hours
To study the inhibitory effect of SR-3029 on β-catenin acetylation
Front Oncol. 2022 Apr 12;12:844477.
OPM2
250 nmol/L
24 hours
Evaluate the anti-myeloma activity of SR-3029 on OPM2 cells, results showed SR-3029 significantly inhibited cell growth and induced apoptosis
Cancer Res. 2023 Dec 1;83(23):3901-3919.
MM.1S
250 nmol/L
24 hours
Evaluate the anti-myeloma activity of SR-3029 on MM.1S cells, results showed SR-3029 significantly inhibited cell growth and induced apoptosis
Cancer Res. 2023 Dec 1;83(23):3901-3919.
H929
250 nmol/L
24 hours
Evaluate the anti-myeloma activity of SR-3029 on H929 cells, results showed SR-3029 significantly inhibited cell growth and induced apoptosis
Cancer Res. 2023 Dec 1;83(23):3901-3919.
T24
25 nM
24 hours
Upregulation of dCK expression
Mol Cancer Ther. 2020 Aug;19(8):1623-1635.
PANC-1
25 nM
24 hours
Upregulation of dCK expression
Mol Cancer Ther. 2020 Aug;19(8):1623-1635.
SR-3029 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NSG mice
Subcutaneous MM.1S tumor xenograft model
Intraperitoneal injection
20 mg/kg
Daily until tumors reached 2,000 mm³ or mice became moribund
Evaluate the anti-myeloma activity of SR-3029 in vivo, results showed SR-3029 significantly inhibited tumor growth and prolonged survival
Cancer Res. 2023 Dec 1;83(23):3901-3919.
Nude mice
Orthotopic models of triple negative breast cancer
Intraperitoneal injection
20 mg/kg
Once daily for 48 days
Significantly inhibited tumor growth and induced tumor cell apoptosis
Sci Transl Med. 2015 Dec 16;7(318):318ra202.
Nude mice
Orthotopic pancreatic tumor model
Intraperitoneal injection
20 mg/kg
Daily for 6 weeks
Inhibited tumor growth and upregulated dCK expression
Mol Cancer Ther. 2020 Aug;19(8):1623-1635.
NPG mice
Patient-derived colorectal tumor xenografts (PDTX) model
Intraperitoneal injection
5 mg/kg
Every 3 days for one month
To evaluate the effect of SR3029 on tumor growth, results showed that SR3029 significantly inhibited tumor growth and increased AES protein expression.
Theranostics. 2021 Mar 4;11(9):4421-4435.
Mouse
Intravenous injection
1 mg/kg
Single dose
Evaluate the pharmacokinetic properties of SR-3029, with an AUC of 6.35 μM·h, a half-life of 0.90 hours, and brain penetration of 12%
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80
SR-3029 动物研究
Animal study
Administered at 20 mg/kg daily via intraperitoneal injection, SR-3029 shows anti-tumor properties in orthotopic MDA-MB-231, MDA-MB-468 (TNBC), SKBR3, and BT474 (HER2+) tumor xenografts without apparent toxicity in mice. The same dosage of SR-3029 also effectively suppresses tumor growth in primary patient-derived xenograft (PDX) models and significantly lowers nuclear β-catenin expression in the tumors of treated mice[2].
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