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Cat. No.: HY-171808

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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.
(Pink: Androgen Receptor ligand (HY-171809); Blue: VHL ligand (HY-125845A); Black: linker (HY-169966)).

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CAS No.: 2798907-16-9
화학식: C₄₅H₅₆F₃N₉O₆S
분자량:908.04

보관:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (279 KB)

ITRI-90 Chemical Structure

CAS No.: 2798907-16-9

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
순도&문서
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

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]. (Pink: Androgen Receptor ligand (HY-171809); Blue: VHL ligand (HY-125845A); Black: linker (HY-169966)).

All PROTACs Isoforms :

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.

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/Enz^R 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/Enz^R cells.
Efficiently reduced both AR-FL and the truncated AR-Vs.

Cell Proliferation Assay^[1]

Cell Line:

VCaP, Enz^R cells
Concentration:

5 and 10 μM
Incubation Time:

24 h
Result:

Inhibits VCaP proliferation when combined with Enzalutamide.
Significantly inhibited Enz^R cells proliferation.

Parmacokinetics

Species	Dose	Route	T_max	C_max
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].

Chemical Information

CAS No. 2798907-16-9
분자량 908.04
화학식 C₄₅H₅₆F₃N₉O₆S
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
선적

Room temperature in continental US; may vary elsewhere.
보관

Please store the product under the recommended conditions in the Certificate of Analysis.

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (279 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Hung CL, et al. Targeting androgen receptor and the variants by an orally bioavailable Proteolysis Targeting Chimeras compound in castration resistant prostate cancer. EBioMedicine. 2023 Apr;90:104500. [Content Brief]

Calculators

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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100 mg

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Biological Activity
- 제품 설명
- In Vitro
- In Vivo
Chemical Information
순도&문서
References

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ITRI-90

All PROTACs Isoforms

Biological Activity

Chemical Information

순도&문서

References

Calculators

Help & FAQs

ITRI-90 Related Classifications

HY-171808 Related Classifications