Olodaterol is a long-acting β₂-adrenoceptor (β₂-AR) agonist.
EC₅₀ for intracellular cAMP increase: 740 pM in human lung fibroblasts (HLF) from control donors; 690 pM in fibroblasts from IPF patients (IPF-LF). [2]

Olodaterol (0.001~10 nM; fibroblasts) hydrochloride initiates growth factor-induced motility and proliferation [2]. Olodaterol (0.1~10 nM; fibroblasts) hydrochloride interferes with FGF-induced phosphorylation of the signaling cascade [2]. Olodaterol (0.001~1000). nM; 30 min; fibroblasts) hydrochloric acid concentration raises intracellular cAMP in a dependent manner. Olodaterol (0 to 10 nM; 30 minutes; fibroblasts) hydrochloric acid concentration reduces the increase in PICP, with maximal effectiveness at 10 nM. Olodaterol hydrochloride exhibits subnanomolar affinity for β2-AR (pKi=9.14 ), olodaterol hydrochloride is selective for this receptor compared with β1-AR and β3-AR subtypes [2].

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In primary human lung fibroblasts (HLF) from control donors and IPF patients (IPF-LF), Olodaterol attenuated TGF-β-induced expression of α-smooth muscle actin (α-SMA) with maximal efficacy of 60% (HLF) and 42% (IPF-LF) at 10 nM. [2]
It concentration-dependently inhibited TGF-β-induced pro-collagen I C-peptide (PICP) increase with maximal efficacy of 70% at 10 nM in both HLF and IPF-LF. [2]
Olodaterol inhibited TGF-β-induced fibronectin release by 65% at 1 nM in both cell types. [2]
Olodaterol blocked TGF-β-induced endothelin-1 (ET-1) release with an IC₅₀ lower than 10 pM and maximal inhibition of 100% (HLF) and 50% (IPF-LF) at 1 nM; this effect was reversed by the β₂-AR antagonist ICI-118,551. [2]
Olodaterol reduced FGF-induced motility in HLF with an IC₅₀ of 4 pM and maximal efficacy of 75% at 100 pM; in IPF-LF, maximal inhibition was reached at 10 nM. [2]
Olodaterol inhibited PDGF-induced motility in HLF with an IC₅₀ of 1 pM and maximal efficacy of 80%; in IPF-LF, the IC₅₀ was 34 pM with 50% inhibition at 10 nM. [2]
Olodaterol attenuated EGF-induced proliferation in HLF with an IC₅₀ of 6 pM and maximal inhibition of ~50% at 100 pM; in IPF-LF, maximal inhibition was 30% at an IC₅₀ of 1.3 pM. [2]
Olodaterol inhibited FGF-induced proliferation in IPF-LF with an IC₅₀ of 10 pM and maximal efficacy of 54% at 1 nM; comparable values were measured for HLF. [2]
At 100 pM, Olodaterol inhibited PDGF-induced proliferation by 40% in HLF and 20% in IPF-LF. [2]
At 10 nM, Olodaterol inhibited TGF-β plus ET-1-induced contraction in collagen gels by approximately 85% in HLF and 47% in IPF-LF. [2]
Olodaterol inhibited FGF-induced phosphorylation of multiple kinases in HLF and IPF-LF, including p-PLCγ1, p-SAPK/JNK, p-c-Raf, p-ERK1/2, p-Akt, and p-p38, with variable inhibition percentages (e.g., p-SAPK/JNK inhibition up to 76% at 10 nM in HLF). [2]

Olodaterol hydrochloride (1 mg/kg; inhalation; day 21) accelerates weight return to control levels (day 21) and attenuates TGF-β-induced pulmonary fibrosis [2]. Olodaterol (0.1 to 3 μg/kg; inhalation; Olodaterol (0.3 and 0.6 μg/kg; inhalation; 24 hours)) induces approximately 60% anesthetic protection after 0.5 hours [3].

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In a bleomycin-induced pulmonary fibrosis mouse model, inhaled Olodaterol (1 mg/mL, once daily, 5 min exposure) administered preventively (days 1–20) or therapeutically (days 7–20) accelerated body weight recovery, significantly reduced total bronchoalveolar lavage fluid (BALF) cell counts (~30%), and significantly decreased levels of TGF-β, MMP-9, TIMP-1, KC, TNF-α, and IL-1β in BALF or lung homogenate. [2]
Preventive Olodaterol treatment significantly attenuated the bleomycin-induced decline in forced vital capacity (FVC) by 45%. Both preventive and therapeutic treatments significantly reduced the increase in relative lung weight and total BALF protein by 33–43%. [2]
In an AAV6.2m-TGF-β1 overexpression model, preventive Olodaterol treatment significantly reduced the influx of monocytes and lymphocytes (~40%), lung density by 36%, relative lung weight and BALF protein by over 50%, and Col3A1 mRNA expression by 37–50%. [2]
Preventive Olodaterol treatment also significantly reduced TGF-β, MMP-9, and TIMP-1 levels in BALF in this model. [2]

Intracellular cAMP levels were measured using a bioluminescent assay. HLF and IPF-LF were pre-incubated with the β₂-AR antagonist ICI-118,551 (30 nM) or the β₁-AR antagonist CGP-20712A (100 nM) for 30 min, followed by stimulation with various concentrations of Olodaterol (1 pM to 1 μM) for another 30 min in the presence of IBMX. cAMP release was then quantified. [2]
For Western blot analysis of phosphorylated kinases, cells were starved, pre-incubated with Olodaterol, and stimulated with FGF (20 ng/mL) for 5 min. Lysates were separated by electrophoresis on Bis-Tris gels and transferred to nitrocellulose membranes. Membranes were blocked and incubated overnight with primary antibodies against phospho-PLCγ1, phospho-SAPK/JNK, phospho-c-Raf, phospho-ERK1/2, phospho-Akt, and phospho-p38, followed by secondary antibodies. Signals were detected via chemiluminescence and quantified by densitometry, normalized to GAPDH. [2]

Western Blot analysis [2]
Cell Types: fibroblasts
Tested Concentrations: 0.1~10 nM
Incubation Duration:
Experimental Results: Interference with FGF-induced signaling cascade phosphorylation.

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Cell proliferation analysis[2]
Cell Types: Fibroblasts
Tested Concentrations: 0.001~10 nM
Incubation Duration:
Experimental Results: Growth factor-induced motility and proliferation were attenuated.

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α-SMA protein expression was measured using a Western blot replacement assay. HLF and IPF-LF were pre-incubated with Olodaterol and stimulated with TGF-β (4 ng/mL) for 48 h. Lysates were added to high-binding plates, incubated with a mouse anti-human α-SMA antibody, followed by an anti-mouse sulfotag antibody, and analyzed using an imager. [2]
Collagen I assembly was assessed using the "scar-in-a-jar" method. Fibroblasts were cultured with Ficoll in DMEM containing L-ascorbic acid 2-phosphate, with or without Olodaterol (10 nM) and TGF-β (5 ng/mL) for 72 h. Cell layers were fixed, blocked, and stained with an anti-collagen I antibody followed by a fluorescent secondary antibody, and mounted with DAPI-containing medium for imaging. [2]
Proliferation was measured by BrdU incorporation. Cells were stimulated with PDGF-BB (50 ng/mL), FGF-basic (20 ng/mL), EGF (3 ng/mL), or FCS (1%) for 72 h, followed by BrdU addition for 18 h, and assessed using a BrdU assay kit. [2]
Cell motility was evaluated by time-lapse microscopy. Cells were stimulated with PDGF-BB (20 ng/mL) or FGF-basic (20 ng/mL) and tracked continuously for approximately 72 h. Manual cell tracking was performed using imaging software, and mean cell movement velocity was calculated. [2]
Collagen gel contraction was assessed using free-floating collagen lattices. Fibroblasts were mixed with bovine type I collagen and polymerized. After polymerization, gels were released, treated with Olodaterol and stimulated with TGF-β (5 ng/mL) plus ET-1 (100 ng/mL) for 72 h. Gel areas were measured by imaging software and normalized to starting area. [2]
ET-1, fibronectin, and pro-collagen I peptide levels in cell supernatants were quantified using ELISA kits. β₂-adrenoceptor protein levels in cell lysates were also measured by ELISA. [2]

Animal/Disease Models: Pulmonary fibrosis C57BL/6 mice
Doses: 1 mg/mL
Route of Administration: inhalation; 21-day
Experimental Results: Accelerated body weight recovery to control level (day 21) and attenuated TGF-β-induced pulmonary fibrosis.

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Animal/Disease Models: guinea pig
Doses: 0.1~3 μg/kg
Route of Administration: inhalation; 5 hrs (hrs (hours))
Experimental Results: Induced dose-dependent bronchial protection.

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Animal/Disease Models: Dog
Doses: 0.3 and 0.6 μg/kg
Route of Administration: Inhalation; 24 hrs (hrs (hours))
Experimental Results: Olodaterol (0.6 μg/kg) induced approximately 60% of maximal bronchial protection after 0.5 hrs (hrs (hours)).

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Male C57BL/6 mice (10–12 weeks old) were used. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (0.5 mg/kg) or adeno-associated virus AAV6.2m-TGF-β1 (2.5×10¹¹ vg). Olodaterol was administered once daily by inhalation in a whole-body exposure chamber using a jet nebulizer for 5 min. The treatment was either preventive (days 1–20) or therapeutic (days 7–20). On day 21, assessments were performed. [2]
Lung density was assessed by micro-computed tomography (μCT) with cardiac gating. Mice were anesthetized, and images were acquired using a μCT system. Hounsfield units were used as a measure of fibrosis. [2]
Lung function was measured using a FlexiVent system. Mice were anesthetized, the trachea was cannulated, and they were ventilated with a tidal volume of 10 mL/kg and an end-expiratory pressure of 3 cmH₂O. Parameters including forced vital capacity (FVC) were analyzed. [2]
After lung function measurement, bronchoalveolar lavage was performed twice with 0.8 mL lavage buffer. Total and differential cell counts were determined. Lungs were weighed, and right lungs were frozen for analysis; left lungs were fixed with 4% paraformaldehyde for histology. [2]
Ashcroft scoring was performed on Masson’s trichrome-stained lung sections using a microscope with a 10× objective, with samples blinded prior to scoring. [2]
Protein levels in BALF and lung homogenates were measured using ELISA kits for TGF-β, MMP-9, TIMP-1, and pro-inflammatory panels. Total protein was quantified using a BCA assay. [2]
RNA was extracted from lung tissues using phenol-chloroform and column-based kits. qRT-PCR was performed using TaqMan assays for Col1A1, Col3A1, and the housekeeping gene PolA2. [2]

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Male C57BL/6 mice (10–12 weeks old) were used. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (0.5 mg/kg) or adeno-associated virus AAV6.2m-TGF-β1 (2.5×10¹¹ vg). Olodaterol was administered once daily by inhalation in a whole-body exposure chamber using a jet nebulizer for 5 min. The treatment was either preventive (days 1–20) or therapeutic (days 7–20). On day 21, assessments were performed. [2]
Lung density was assessed by micro-computed tomography (μCT) with cardiac gating. Mice were anesthetized, and images were acquired using a μCT system. Hounsfield units were used as a measure of fibrosis. [2]
Lung function was measured using a FlexiVent system. Mice were anesthetized, the trachea was cannulated, and they were ventilated with a tidal volume of 10 mL/kg and an end-expiratory pressure of 3 cmH₂O. Parameters including forced vital capacity (FVC) were analyzed. [2]
After lung function measurement, bronchoalveolar lavage was performed twice with 0.8 mL lavage buffer. Total and differential cell counts were determined. Lungs were weighed, and right lungs were frozen for analysis; left lungs were fixed with 4% paraformaldehyde for histology. [2]
Ashcroft scoring was performed on Masson’s trichrome-stained lung sections using a microscope with a 10× objective, with samples blinded prior to scoring. [2]
Protein levels in BALF and lung homogenates were measured using ELISA kits for TGF-β, MMP-9, TIMP-1, and pro-inflammatory panels. Total protein was quantified using a BCA assay. [2]
RNA was extracted from lung tissues using phenol-chloroform and column-based kits. qRT-PCR was performed using TaqMan assays for Col1A1, Col3A1, and the housekeeping gene PolA2. [2]

Effects During Pregnancy and Lactation
◉ Overview of Drug Use During Lactation
While there is currently no published data on the use of olodaterol during lactation, data on the related drug terbutaline suggest that very small amounts are expected to be excreted into breast milk. The authors of several reviews agree that the use of such drugs during lactation is acceptable due to the low bioavailability of inhaled bronchodilators and the low maternal serum concentrations after administration. ◉ Effects on Breastfed Infants
No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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[1]. Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists. Bioorg Med Chem. 2020;28(1):115178.

[2]. Olodaterol shows anti-fibrotic efficacy in in vitro and in vivo models of pulmonary fibrosis. Br J Pharmacol. 2017;174(21):3848-3864.

[3]. Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models [published correction appears in J Pharmacol Exp Ther. 2013 Jul;346(1):161]. J Pharmacol Exp Ther. 2010;334(1):53-62.

Olodaterol hydrochloride is a hydrochloride salt composed of olodaterol and an equivalent amount of hydrochloric acid. It is used for the long-term treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (including chronic bronchitis and/or emphysema). It is a beta-adrenergic agonist and bronchodilator. It contains olodaterol (1+).
See also: Olodaterol (with active fraction); Olodaterol hydrochloride; Tiotropium bromide (ingredient)... See more...

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Drug Indications
Treatment of cystic fibrosis

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Olodaterol (Striverdi®) is a long-acting β₂-adrenoceptor agonist approved for once-daily maintenance treatment of chronic obstructive pulmonary disease (COPD). This study demonstrates its anti-fibrotic properties in both in vitro and in vivo models of pulmonary fibrosis, suggesting potential therapeutic benefit for idiopathic pulmonary fibrosis (IPF). [2]
In IPF fibroblasts and bleomycin-challenged mouse lungs, β₂-adrenoceptor expression was reduced, which may affect compound efficacy. [2]
The anti-fibrotic effects were more pronounced with preventive dosing regimens in animal models, supporting a role in inhibiting early fibroblast activation. [2]

C21H27CLN2O5

422.906

422.161

C, 59.64; H, 6.44; Cl, 8.38; N, 6.62; O, 18.92

869477-96-3

Olodaterol;868049-49-4

11711522

White to light yellow solid powder

3.654

5

6

7

29

521

1

[C@H](C1C=C(O)C=C2NC(COC=12)=O)(O)CNC(C)(C)CC1C=CC(OC)=CC=1.Cl

KCEHVJZZIGJAAW-FERBBOLQSA-N

InChI=1S/C21H26N2O5.ClH/c1-21(2,10-13-4-6-15(27-3)7-5-13)22-11-18(25)16-8-14(24)9-17-20(16)28-12-19(26)23-17;/h4-9,18,22,24-25H,10-12H2,1-3H3,(H,23,26);1H/t18-;/m0./s1

6-hydroxy-8-[(1R)-1-hydroxy-2-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one;hydrochloride

Olodaterol hydrochloride BI 1744 BI1744BI-1744 Olodaterol StriverdiOlodaterol HCl

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~250 mg/mL (~591.16 mM)

Solubility in Formulation 1: 14.29 mg/mL (33.79 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)