2. Vitamin D Related/Nuclear Receptor PROTAC Apoptosis
  3. Androgen Receptor PROTACs Apoptosis
  4. ITRI-90

ITRI-90 is an orally active androgen receptor (AR) PROTAC degrader. ITRI-90 effectively degrades both full-length AR (AR-FL) and the splice variant AR-V7 protein via the ubiquitin-proteasome system, thereby inhibiting AR transcriptional activity and the target gene expression. ITRI-90 significantly inhibits the proliferation of prostate cancer cells and induces apoptosis, include Enzalutamide-resistant growth cell. ITRI-90 exhibits favorable pharmacokinetic properties and demonstrates potent antitumor efficacy in vivo. ITRI-90 can be used for prostate cancer research.

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ITRI-90

ITRI-90 Chemical Structure

CAS No. : 2798907-16-9

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ITRI-90 Related Antibodies

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Description

ITRI-90 is an orally active androgen receptor (AR) PROTAC degrader. ITRI-90 effectively degrades both full-length AR (AR-FL) and the splice variant AR-V7 protein via the ubiquitin-proteasome system, thereby inhibiting AR transcriptional activity and the target gene expression. ITRI-90 significantly inhibits the proliferation of prostate cancer cells and induces apoptosis, include Enzalutamide-resistant growth cell. ITRI-90 exhibits favorable pharmacokinetic properties and demonstrates potent antitumor efficacy in vivo. ITRI-90 can be used for prostate cancer research[1].

In Vitro

ITRI-90 (0-20 μM,24 h) reduces AR-FL and AR-V(ΔLBD) proteins in LNCaP, CWR22Rv1, VCaP cells (with DC50 = 2.12, 5.73 and 8.67 nM for AR-FL proteins and DC50 = 4.72 and 0.29 nM for AR-V proteins in CWR22Rv1, VCaP cells respectively) [1].
ITRI-90 (10 μM, 24 h) demonstrates a prolonged duration of effect, enabling less frequent dosing in LNCaP, CWR22Rv1 and VCaP cells[1].
ITRI-90 (10 μM, 6 or 10 h) degrades AR protein levels via ubiquitin-proteasome dependent system in CWR22Rv1 and ITRI-126, cells[1].
ITRI-90 (0.1-1 μM,24 h) less efficiently inhibits AR target expression on both AR and AR-V7 signaling and exerts AR inhibition mediated via NTD-targeted protein degradation or direct blockade of ligand binding in LNCaP and CWR22Rv1 cells[1].
ITRI-90 (0.001-100 μM, 24 h or 7 days) specifically and effectively inhibits cancer cell proliferation and induces apoptosis in LNCaP, CWR22Rv1 and VCaP cells[1].
ITRI-90 (5 or 10 μM, one day ) effectively degrades Enzalutamide (HY-70002)-induced AR-FL and truncated AR V(ΔLBD) proteins in both short-term treated and long term acquired resistant cells, thereby significantly impairing the enzalutamide-resistant cell growth in VCaP, C4-2B and C4-2B/EnzR cells[1].
ITRI-90 shows low plasma clearance rate (6.62 mL/min/kg) and achieves well actual body exposure (AUC/Dose = 2502.4) in mouse liver microsomes[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ITRI-90 Related Antibodies

Western Blot Analysis[1]

Cell Line: LNCaP, CWR22Rv1, VCaP cells
Concentration: 0, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 and 20 μM
Incubation Time: 24 h
Result: Effectively reduced AR-FL and AR-V(ΔLBD) proteins in a dose-dependent manner.

Western Blot Analysis[1]

Cell Line: LNCaP, CWR22Rv1, VCaP cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Displayed different kinetics of degradation and sustainability after drug washout at different time.
Achieved AR and AR-V(ΔLBD) degradation by 24 h treatment.
Appeared to sustain low pro tein levels up to 24 h after drug washout.

Western Blot Analysis[1]

Cell Line: CWR22Rv1 and 293T cells
Concentration: 10 μM
Incubation Time: 6 or 10 h
Result: Degradation of AR and AR-V(ΔLBD) was recovered by MG132 and MLN4924 treatment.
Showed AR proteins strongly ubiquitinated.

Cell Proliferation Assay[1]

Cell Line: LNCaP, CWR22Rv1, VCaP cells
Concentration: 0.001, 0.01, 0.1, 1, 10 and 100 μM
Incubation Time: 7 days
Result: Strongly inhibited cell growth by over 90% with IC50s = 6.587, 4.134, 5.454 μM for LNCaP, CWR22Rv1, VCaP cells, respectively.
Activated caspase 3/7 within 24 h.

Real Time qPCR[1]

Cell Line: LNCaP and CWR22Rv1 cells
Concentration: 0.1 and 1μM
Incubation Time: 24 h
Result: Decreased KLK3, NKX3.1 and TMPRSS2 expression in LNCaP and CWR22Rv1 cells.
Reduced CCNA2, CDC20, CDK1, UBE2C, UGT2B17 and EDN2 in CWR22Rv1 cells.

Cell Proliferation Assay [1]

Cell Line: LNCaP, CWR22Rv1, VCaP cells
Concentration: 0.001, 0.01, 0.1, 1, 10 and 100 μM
Incubation Time: 7 days
Result: Strongly inhibited cell growth by over 90% for LNCaP, CWR22Rv1 and VCaP cells with IC50s = 6.587, 4.134 and 5.454 μM.

Apoptosis Analysis[1]

Cell Line: LNCaP, CWR22Rv1, VCaP cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Rapidly activated caspase 3/7.

Western Blot Analysis[1]

Cell Line: VCaP, C4-2B/EnzR cells cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Reversed AR degraders significantly in VCaP cell.
Displayed Enzalutamide resistance as well as elevated AR-FL and AR-V7 in Long-term drug exposure of C4-2B Cells resulted in C4-2B/EnzR cells.
Efficiently reduced both AR-FL and the truncated AR-Vs.

Cell Proliferation Assay[1]

Cell Line: VCaP, EnzR cells
Concentration: 5 and 10 μM
Incubation Time: 24 h
Result: Inhibits VCaP proliferation when combined with Enzalutamide.
Significantly inhibited EnzR cells proliferation.
Parmacokinetics
Species Dose Route Tmax Cmax
Mice[1] 10 mg/kg p.o. 1.5 h 3945 ng/mL
In Vivo

ITRI-90 (10 mg/kg, i.p., twice daily for 15 days) significantly impairs the tumor growth without obvious toxicities in tumor regression of the CWR22Rv1 xenograft mice model[1].
ITRI-90 (100 mg/kg, p.o., twice daily for 21 days) is an orally available degrader specifically targeting AR-FL and LBD-truncated AR-Vs in tumor regression of the CWR22Rv1 xenograft mice model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: CWR22Rv1 cells (5 × 106) induced-male C.B-17 SCID mice (4-6 weeks)[1]
Dosage: 10 mg/kg
Administration: twice daily for 15 days
Result: Significantly impaired the tumor growth without obvious toxicities[1].
Reached an average tumor growth inhibition (TGI) of 76.64% on day 12[1].
Significantly decreased AR-FL 12 and AR-V protein levels in tumors detected at the final time point[1].
Animal Model: CWR22Rv1 cells (5 × 106) induced-male C.B-17 SCID mice (4-6 weeks)[1]
Dosage: 100 mg/kg
Administration: p.o., twice daily for 21 days
Result: Observed significant tumor suppression with an average TGI of 71.73 % without obvious toxicity[1].
Reduced protein levels of AR-FL and AR Vs in the tumors[1].
Molecular Weight

908.04

Formula

C45H56F3N9O6S
CAS No.
SMILES

FC(F)(C1=NN=C2N1N=C(N3CCC(C4=CC=C(C=C4)OCCCCOCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@@H](C5)O)C(NCC6=CC=C(C7=C(N=CS7)C)C=C6)=O)=O)=O)CC3)CC2)F
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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ITRI-90 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ITRI-902798907-16-9ITRI90ITRI 90Androgen ReceptorPROTACsApoptosisAR PROTAC degraderapoptosis Enzalutamide-resistantprostate cancerInhibitorinhibitorinhibit

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