GLPBio

TDRL-551

Catalog No.: GC64542Purity:>98.00%
COASDSData Sheet
TDRL-551 هو مثبط قوي لبروتين A (RPA) (IC50 = 18 ميكرومتر)يثبط TDRL-551 تفاعل RPA-DNA ويزيد من فعالية العلاج الكيميائي القائم على البلاتين (Pt) في سرطان الرئة والمبيضيلعب RPA أدوارًا أساسية في كل من إصلاح ختان النوكليوتيدات (NER) وإعادة التركيب المتماثل (HR) ، إلى جانب دوره في تكرار الحمض النووي وتفعيل نقطة تفتيش تلف الحمض النووي

المنتجات مخصصة للاستخدام البحثي فقط، وليست للاستخدام البشري. نحن لا نبيع للمرضى.

TDRL-551
Cas No.: 1644626-43-6
1mgIn Stock
$85.00
1
5 mgIn Stock
$234.00
1
10 mgIn Stock
$342.00
1
25 mgIn Stock
$720.00
1
50 mgIn Stock
$1,152.00
1
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المراجع (Citations)

لا تتوفر حاليًا مراجع لهذا المنتج. فيما يلي مجموعة مختارة من المنشورات التي تستشهد بمنتجات GlpBio.
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    641, 529–536 (2025)
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    628, 630–638 (2024)
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    632, 686–694 (2024)
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    Nature
    618, 1017–1023 (2023)
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    Nature
    610, 366–372 (2022)
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    Cell
    187(9):2288-2304 (2024)
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    Cell
    183(7):1867-1883 (2020)
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    388(6745) (2025)
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    33, 904–922 (2023)
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    31, 1291–1307 (2021)

الوصف (Description)

TDRL-551 is a potent inhibitor of replication protein A (RPA) with an IC50 value of 18µM[1]. RPA is an important single-stranded DNA (ssDNA) binding protein complex in eukaryotes and plays an important role in multiple key biological processes such as DNA replication, repair, damage response, telomere maintenance and viral defense[2, 3]. TDRL-551 can inhibit RPA-DNA interaction and improve the efficacy of platinum-based chemotherapy for lung and ovarian cancer[4].

In vitro, TDRL-551 (0-200μM) treatment of H460, SKOV-3, A2780 and OVCA-429 cells for 48h inhibited cell viability in a dose-dependent manner[1]. TDRL-551 (0-20μM) treatment of human non-small cell lung cancer cell line H460 cells for 24h induced cell death in a dose-dependent manner, but without caspase activation, indicating that TDRL-551-induced cell death is a non-apoptotic mechanism[5].

In vivo, TDRL-551 (200mg/kg) was intraperitoneally injected into mice bearing non-small cell lung cancer (NSCLC) cell xenografts for 20 days, significantly inhibiting tumor growth in the mice, with an effect comparable to that of carboplatin. The combination of the two had a better effect[6].

References:
[1] Mishra A K, Dormi S S, Turchi A M, et al. Chemical inhibitor targeting the replication protein A–DNA interaction increases the efficacy of Pt-based chemotherapy in lung and ovarian cancer[J]. Biochemical pharmacology, 2015, 93(1): 25-33.
[2] Dueva R, Iliakis G. Replication protein A: a multifunctional protein with roles in DNA replication, repair and beyond[J]. NAR cancer, 2020, 2(3): zcaa022.
[3] Zou Y U E, Liu Y, Wu X, et al. Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses[J]. Journal of cellular physiology, 2006, 208(2): 267-273.
[4] Gavande N S, VanderVere-Carozza P S, Hinshaw H D, et al. DNA repair targeted therapy: The past or future of cancer treatment?[J]. Pharmacology & therapeutics, 2016, 160: 65-83.
[5] VanderVere-Carozza P S, Gavande N S, Jalal S I, et al. In vivo targeting replication protein A for cancer therapy[J]. Frontiers in Oncology, 2022, 12: 826655.
[6] Mishra A K. Developing small molecule inhibitors targeting Replication Protein A for platinum-based combination therapy[D]. , 2014.

البروتوكول (Protocol)

Cell experiment [1]:

Cell lines

H460 cells

Preparation Method

H460 cells were plated at 5×103 cells/well in black 96-well plates with clear bottoms (Costar) and incubated for 24h prior to treatments. Cells were treated with 0-20μM TDRL-551 for 24h. Apoptosis induction was determined by activation of Caspases 3 and 7 using the CellEvent™ Caspase-3/7 Green Detection Reagent (Invitrogen).

Reaction Conditions

0-20μM; 24h

Applications

TDRL-551-induced cell death was not accompanied by caspase activation, suggesting that cell death is a non-apoptotic mechanism.

Animal experiment [2]:

Animal models

NOD/SCID mice

Preparation Method

Sixty mice aged 8-10 weeks were implanted in the hind flank with 2×106 H460 NSCLC cells in Matrigel. Tumor volume was measured with a caliper. Eight days after implantation, mice with tumor sizes ranging from 32-152.5mm3 were randomized into four treatment groups. Carboplatin was dissolved in water and administered intraperitoneally at a dose of 50mg/kg on days 8, 14, and 20 after implantation. TDRL-551 was suspended in 20% DMSO, 10% Tween 80, and 70% PBS and injected intraperitoneally at a dose of 200mg/kg on days 8, 10, 14, 17, and 20. The control group was a group that did not receive the designated treatment. Tumor volume was monitored every two weeks and the results are expressed as the mean tumor volume ± standard error of the mean for each group.

Dosage form

200mg/kg; on days 8, 10, 14, 17, 20; i.p.

Applications

Carboplatin treatment and TDRL-551 showed similar tumor growth inhibition effects. The difference in tumor volume between the combination treatment and TDRL-551 monotherapy was statistically significant at all data points after day 14.

References:
[1] VanderVere-Carozza P S, Gavande N S, Jalal S I, et al. In vivo targeting replication protein A for cancer therapy[J]. Frontiers in Oncology, 2022, 12: 826655.
[2]Mishra A K. Developing small molecule inhibitors targeting Replication Protein A for platinum-based combination therapy[D]. , 2014.

وثائق المنتج (Product Documents)

Purity:>98.00%Appearance:A solid
COASDSData Sheet

الخصائص الكيميائية (Chemical Properties)

رقم CAS
1644626-43-6
الصيغة الجزيئية
C25H23ClIN3O4
الوزن الجزيئي
591.83
الذوبانية
DMSO : 62.5 mg/mL (105.60 mM; Need ultrasonic)
التخزين
Store at -20°C
إرشادات عامة
اختر مذيبًا مناسبًا وفقًا لبيانات ذوبانية المنتج. بعد التحضير، قسّم المحلول المخزون إلى أجزاء لتجنب دورات التجميد والذوبان المتكررة.
استخدم المحاليل المخزونة خلال 6 أشهر عند حفظها في -80°C، أو خلال شهر واحد عند حفظها في -20°C.
لتحسين الذوبانية، سخّن الأنبوب إلى 37°C وعرّضه للموجات فوق الصوتية لمدة مناسبة.
شروط الشحن
تُشحن عينات التقييم مع عبوات تبريد. وتُشحن الأحجام الأخرى المتاحة في درجة حرارة الغرفة، أو مع عبوات تبريد عند الطلب.

الحاسبات (Calculators)المولارية / التخفيف / الوزن الجزيئي / تحويل الوحدات / تركيبة داخل الجسم الحي / الذوبانية

g/mol

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