2. Neuronal Signaling
  3. Amyloid-β
  4. rTRD01

rTRD01 is an orally active, specific TDP-43 binder that targets the RRM1 and RRM2 domains of TDP-43. rTRD01 partially disrupts the interaction between TDP-43 and c9orf72 repeat RNA, but does not affect the binding of TDP-43 to canonical binding sequences. rTRD01 exhibits significant neuroprotective effects in zebrafish models, improves motor function and protects against paraquat (a widely used herbicide)-induced neurodegeneration, with no teratogenicity at high concentrations. rTRD01 is not a general antioxidant and cannot counteract Rotenone (HY-B1756)-induced neuronal death. rTRD01 can be used to study amyotrophic lateral sclerosis and other TDP-43 proteinopathies.

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rTRD01

rTRD01 Chemical Structure

CAS No. : 1332175-56-0

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10 mM * 1 mL in DMSO
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Based on 1 publication(s) in Google Scholar

rTRD01 Related Antibodies

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Description

rTRD01 is an orally active, specific TDP-43 binder that targets the RRM1 and RRM2 domains of TDP-43. rTRD01 partially disrupts the interaction between TDP-43 and c9orf72 repeat RNA, but does not affect the binding of TDP-43 to canonical binding sequences. rTRD01 exhibits significant neuroprotective effects in zebrafish models, improves motor function and protects against paraquat (a widely used herbicide)-induced neurodegeneration, with no teratogenicity at high concentrations. rTRD01 is not a general antioxidant and cannot counteract Rotenone (HY-B1756)-induced neuronal death. rTRD01 can be used to study amyotrophic lateral sclerosis and other TDP-43 proteinopathies[1][2].

IC50 & Target

Kd: 89 uM (TDP-43102–269)[1]
In Vitro

rTRD01 (500 μM) binds specifically to recombinantly purified human TDP-43(102-269)-His protein[1].
rTRD01 (0.03 μM-1 mM) binds to recombinantly purified human TDP-43(102-269)-His protein with an apparent dissociation constant of 89.4 μM, as measured by MST[1].
rTRD01 (0.01 mM-1 mM; 30 min pre-incubation with TDP-43 proteins, 90 min incubation with RNA) selectively inhibits the interaction of recombinantly purified human TDP-43 proteins with disease-linked (GGGGCC)4 c9orf72 RNA, with an IC50 of ~150 μM for TDP-43(102-269)-His, while sparing interactions with canonical (UG)6 RNA[1].
rTRD01 binds to the RNA recognition motifs of human TDP-43 and partially disrupts its interaction with disease-associated (GGGGCC)4 RNA[2].

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

rTRD01 Related Antibodies
In Vivo

rTRD01 (20 μM; feeding; single exposure) significantly reduces ALS-like locomotor defects in Drosophila larvae expressing TDP-43G298S mutant, decreasing larval turning time from 19.3 s-12.3 s[1].
rTRD01 (10-75 μM; incubated in E3 medium; starting at 12 hpf) protects against paraquat-induced neurodegeneration in zebrafish embryos by a non-general antioxidant mechanism, as evidenced by rescue of spinal curvature and brain morphology metrics with no effect on rotenone-induced neuronal death[2].

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

Animal Model: D42 GAL4 driver line (crossed with w1118 genetic background control, or lines expressing human TDP-43G298S/TDP-43WT; motor neuron expression of human G298S mutant TDP-43 via GAL4-UAS system)[1]
Dosage: 20 μM
Administration: feeding; single exposure
Result: Reduced larval turning time in TDP-43G298S-expressing larvae from 19.3 s to 12.3 s.
Showed no significant improvement in larval turning time in TDP-43WT-expressing larvae.
Animal Model: Tübingen driver line (TDL6)[2]
Dosage: 10 μM, 25 μM, 50 μM, 75 μM
Administration: incubated in E3 medium; starting at 12 hpf; media refreshed every 24 hours (co-treatment); washed at 18 hpf (sequential treatment)
Result: Reduced spine deformity prevalence from ~70% with paraquat alone to ~10% with 50 μM rTRD01 co-treatment or sequential treatment.
Eliminated statistically significant reductions in brain cross-sectional area, mean fluorescence, and fluorescence density caused by paraquat alone with 50 μM rTRD01 co-treatment.
Showed no protective effect against rotenone-induced gray brain phenotype at doses of 10, 25, 50, or 75 μM.
Was well-tolerated up to 75 μM, with no discernable morphological defects and >90% survival through 5 dpf at all tested doses.
Molecular Weight

344.38

Formula

C18H21FN4O2
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(C1=CN=CC(N2CCCC(CC3=CC=C(C=C3)F)(C2)CO)=N1)N
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (290.38 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.9038 mL 14.5188 mL 29.0377 mL
5 mM 0.5808 mL 2.9038 mL 5.8075 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.9038 mL 14.5188 mL 29.0377 mL 72.5942 mL
5 mM 0.5808 mL 2.9038 mL 5.8075 mL 14.5188 mL
10 mM 0.2904 mL 1.4519 mL 2.9038 mL 7.2594 mL
15 mM 0.1936 mL 0.9679 mL 1.9358 mL 4.8396 mL
20 mM 0.1452 mL 0.7259 mL 1.4519 mL 3.6297 mL
25 mM 0.1162 mL 0.5808 mL 1.1615 mL 2.9038 mL
30 mM 0.0968 mL 0.4840 mL 0.9679 mL 2.4198 mL
40 mM 0.0726 mL 0.3630 mL 0.7259 mL 1.8149 mL
50 mM 0.0581 mL 0.2904 mL 0.5808 mL 1.4519 mL
60 mM 0.0484 mL 0.2420 mL 0.4840 mL 1.2099 mL
80 mM 0.0363 mL 0.1815 mL 0.3630 mL 0.9074 mL
100 mM 0.0290 mL 0.1452 mL 0.2904 mL 0.7259 mL
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rTRD01 Related Classifications

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:

rTRD011332175-56-0rTRD 01rTRD-01Amyloid-ββ-amyloid peptideAβAbetaTDP-43 RRM1(GGGGCC)4 RNAhuman TDP-43 102 - 269 -His proteinTDP-43 proteinopathiesamyotrophic lateral sclerosisTDP-43 RRM2Drosophila larvae(UG)6 canonical binding sequencec9orf72 hexanucleotide RNA repeatzebrafish
Inhibitorinhibitorinhibit

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