Preclinical pharmacological profile of nomegestrol acetate, a synthetic 19-nor-progesterone derivative
© van Diepen; licensee BioMed Central Ltd. 2012
Received: 22 June 2012
Accepted: 30 August 2012
Published: 8 October 2012
Nomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-nor-progesterone, recently completed clinical trials for use with 17beta-estradiol in a new monophasic combined oral contraceptive. In this review, published as well as previously unpublished preclinical studies that detail the effects of NOMAC on estrogenic, progestogenic, and androgenic systems, as well as mineralocorticoid, glucocorticoid, bone, and metabolic indices are described.
In vitro assays to determine NOMAC structure-activity relationships used tissue derived from rat uteri. Transactivation profiles were performed using Chinese hamster ovary (CHO) cells transfected with cDNAs encoding human steroid receptors. Estrogenic and anti-estrogenic activities were monitored in vivo in rats as well as in vitro in human breast cancer cells. Standard in vivo techniques were used in rats to determine progestational activity; antigonadotropic, androgenic, mineralocorticoid, and glucocorticoid activities; as well as effects on bone and other metabolic indices. Ovulation inhibition was monitored in rats and primates. NOMAC’s effects on cardiovascular systems were determined in dogs and primates.
NOMAC was without significant agonistic or antagonistic activity for estrogen receptor alpha or beta in vitro, and inhibited ovulation in rats and monkeys (2.5 mg/kg and 1 mg/kg, respectively). NOMAC lacked androgenic, antimineralocorticoid, glucocorticoid, and metabolic activity and exhibited moderate anti-androgenic activity in rats. NOMAC did not affect bone mineral density (BMD) in rats or hemodynamic and electrophysiologic parameters in dogs and primates.
NOMAC is a selective progestogen structurally similar to progesterone that has modest anti-androgenic activity and does not affect lipid or carbohydrate metabolism, BMD, or many cardiovascular parameters in selected animal models.
KeywordsNomegestrol acetate (NOMAC) Progesterone Oral contraceptives Preclinical studies Pharmacology
In this article, we present both previously published and unpublished data to deliver a complete preclinical pharmacological profile of NOMAC. The studies were approved by the review board for animal experimentation at Merck Sharp & Dohme (MSD, Oss, The Netherlands) or at Theramex (Monaco) and were performed in accordance with the principles and procedures described in the European Union guidelines for the care and use of laboratory animals. Data are reported as ± standard error of the mean unless otherwise indicated. Comparisons between groups were analyzed using analysis of variance (ANOVA) models, unless otherwise indicated and statistical significance was defined as P<0.05.
In vitroprogestogenic activity
The in vitro progestogenic activity of NOMAC was initially assessed by studying its structure-activity relationship with specific ligands on several cytosolic steroid receptors . The relative binding affinity (RBA) of NOMAC for the rat uterine progesterone receptor (PR) is very similar to the binding affinity of progesterone. After 2 and 24 hours of incubation with rat uterine PR, the RBA of NOMAC (relative to progesterone) was 72% and 92%, respectively.
Duc et al. determined the apparent binding constant at equilibrium (k d ), maximum concentration of binding sites (B max ), the dissociation rate constant k −1 , and the specific RBA (relative to progesterone) of radiolabeled NOMAC to PR derived from the uteri of estrogen-primed rats. In their studies, NOMAC had high specificity for rat uterine PR; saturation occurred at approximately 30 nM. Nonspecific binding was very low, accounting for only 5-7% of total binding. Determination of the specific binding constants indicated that NOMAC had a k d and B max of 5.44 ± 1.27 nmol/L and 1.51 ± 0.11 pmol/mg protein, respectively. In addition, it was determined that NOMAC binds avidly, but is slow to dissociate from rat uterine PR (k −1 = 4.9 ± 0.5 × 10–5 s–1).
Receptor-binding experiments, although useful, do not distinguish between agonistic and antagonistic activity. van Diepen et al. used established cellular assays [14–16] to determine the agonistic and antagonistic profiles of NOMAC, levonorgestrel (LNG), drospirenone (DRSP), dienogest (DNG), and progesterone in Chinese hamster ovary (CHO)-K1 cells that were stably transfected with cDNAs encoding human receptors, including progesterone receptor B (hPRB), androgen receptor (hAR), mineralocorticoid receptor (hMR), glucocorticoid receptor (hGR), and estrogen receptors (ER) α and β (hERalpha and hERbeta, respectively). NOMAC and LNG were the most potent progestogens in activating hPRB in CHO cells. NOMAC did not display antagonistic activity against hPRB. NOMAC, DRSP, DNG, LNG, and progesterone were all capable of antagonizing hAR. None of the progestogens tested (including NOMAC) activated or antagonized hERalpha, hERbeta, or hGR or were hMR agonists. In addition, NOMAC did not have antimineralocorticoid activity. These experiments support the overall conclusion that NOMAC has a progestational profile that is similar to progesterone.
In vivoprogestational activity
Progestogens antagonize estrogen action by induction of estradiol metabolism and down-regulation of the ER [17–20]. Progesterone down-regulation of the ER and the agonistic versus antagonistic effect of progesterone on uterine weight is dependent on the concentration of plasma E2 . Moreover, progesterone is far more effective in reducing ER levels in estrogen-primed tissue .
The effects of NOMAC treatment on the expression of cytosolic uterine ER were studied in Sprague–Dawley ovariectomized (OVX) rats. After recovering from ovariectomy for at least 15 days, each rat received an intraperitoneal injection of vehicle or E2 (5 μg/rat). After 24 hours, each rat received either vehicle (n = 8), E2 only (n = 6), E2 + progesterone (100, 250, or 950 μg/rat; n = 5 per dose), E2 + NOMAC (100, 250, or 950 μg/rat; n = 5 per dose), or E2 + medroxyprogesterone acetate (MPA; 100, 250, or 950 μg/rat; n = 5 per dose). After an additional 24 hours, the rats were killed and uteri removed. ER contained in nuclear cell fractions originating from rat uterine cytosol were determined using a 3[H] E2 exchange assay [21, 23].
Antigonadotropic activity and ovulation inhibition
Paris et al. and van Diepen  investigated the ability of NOMAC to inhibit ovulation in the rat. After 3 consecutive, regular 4-day cycles, animals in the metestrus phase received single subcutaneous injections of NOMAC or progesterone at doses of 0.25, 1, or 4 mg (n = 5-6 per dosage group) or vehicle (n = 17). In this study, the rate of ovulation in the vehicle-treated control animals was 76.5%. At the lowest dose (0.25 mg/rat), NOMAC inhibited ovulation in 78.2% (5/6) of rats, indicating that the 50% inhibition dose (ID50) for NOMAC was <1.25 mg/kg. The ID50 for progesterone was approximately 5 mg/kg. Oral NOMAC produced similar results and suggested that oral NOMAC is at least 2 times more potent than oral LNG in inhibiting ovulation in rats. In Cynomolgus monkeys (Macaca fascicularis), which have a menstrual cycle very similar to the human menstrual cycle (average Cynomolgus cycle length, 29 days; range, 26-32 days), NOMAC was also able to inhibit ovulation. NOMAC administered for 1 cycle to 34 Cynomolgus monkeys provided effective, dose-dependent inhibition of ovulation, which was observed in 4/11, 7/10, and 11/11 monkeys (0.10, 0.25, and 1.00 mg/kg/day NOMAC, respectively) . The ID50 of NOMAC was 0.14 mg/kg. Treatment with NOMAC did not influence body weight or cycle length relative to nontreatment.
In vitroestrogenic and anti-estrogenic activity
Estrogens stimulate proliferation of human breast tumor cells . However, the effect of progestogens on human breast tumor cells is more controversial. Progestogens that interact with the ER can have a stimulatory effect growth of T-47D and MCF-7 cells , whereas progestogens that do not interact with ER do not stimulate cell proliferation. To determine the effect of NOMAC on breast cancer cell growth, in the absence of E2, Catherino et al. investigated the effect of NOMAC and megestrol acetate (MAC) on growth of MCF-7 and T-47D cells. The cells were incubated for 6 days in the presence of NOMAC or MAC at doses up to 10–6 M and the proliferative activity of cells grown in the presence of progestogen was determined (measured by total DNA). As would be expected of progestogens that do not activate ER, NOMAC and MAC at doses up to 1 μM/L did not increase proliferative activity.
Although NOMAC has no growth-stimulating activity on breast cancer cells in the absence of E2, some evidence suggests that it may also help attenuate the proliferative effects of endogenous E2 by preventing E2 formation from estrone sulfate (E1S) and by enhancing the conversion of E2 to less potent metabolites. In support of this possibility, NOMAC was able to inhibit estrone sulfatase and 17β-hydroxysteroid dehydrogenase activity, 2 enzymes responsible for the conversion of E1S to E2 . In T-47D cells, NOMAC (5 × 10–6 M and 5 × 10–5 M) blocked the conversion of E1S (2 × 10–6 M) to E2 by –60% and –71%, respectively. In MCF-7 cells, NOMAC (5 × 10–6 M and 5 × 10–5 M) blocked the conversion of E1S (5 × 10–9 M) to E2 by –43% and –77%, respectively.
NOMAC also had a stimulatory effect on the activity of estrogen sulfotransferase, an enzyme that converts E1 to E1S or E2 to E2S in hormone-dependent MCF-7 and T-47D human breast cancer cells . At concentrations of 5 × 10–8 M and 5 × 10–7 M, NOMAC increased the activity of sulfotransferase in MCF-7 cells by 60.6% and 83%, respectively. In T-47D cells, NOMAC (5 × 10–7 M) increased estrogen sulfotransferase activity by 69.2%. Taken together, these studies indicate that NOMAC alone does not induce breast cancer cell growth in vitro and may reduce the proliferative effect of E2 in these cells by preventing conversion of E1S to more potent E2.
In vivoestrogenic and anti-estrogenic activity
Effect of progesterone, MPA, and NOMAC on the uterine weight in estradiol-benzoate-treated mice
No. of mice
Subcutaneous administration a
21.61 ± 1.37**
32.88 ± 2.26
32.04 ± 1.38
30.46 ± 1.53
29.78 ± 2.99
27.50 ± 1.08
24.92 ± 2.37*
29.34 ± 2.42
27.16 ± 3.22
23.72 ± 1.08**
23.94 ± 1.16**
Oral administration a
12.31 ± 0.49
40.99 ± 2.11
30.08 ± 3.92*
22.39 ± 3.09**
24.70 ± 2.27**
46.74 ± 4.48
29.22 ± 1.89**
30.97 ± 2.47**
25.07 ± 2.28**
25.09 ± 4.37**
Androgenic and anti-androgenic activity
Several studies have demonstrated that NOMAC is devoid of androgenic activity [1, 13, 30, 31]. In some of the initial experiments to examine androgenic activity, sexually immature, castrated male rats were treated with a high dose of NOMAC (10 mg/rat) for 10 days; it did not increase the weights of male accessory sex organs  or have other androgenic or anabolic effects . Although these studies showed that NOMAC did not possess androgenic activity in rats, it did have significant anti-androgenic activity, which was estimated to be between 3 to 5 times greater than that of chlormadinone acetate (CMA) . In transactivation studies, NOMAC was also found to be an effective antagonist against hAR , with much greater anti-androgenic activity than progesterone, DNG, and DRSP, but less activity than LNG. These results were consistent with previous findings demonstrating that the binding affinity of NOMAC for rat androgen receptor was approximately 4 times greater than that of progesterone .
Glucocorticoid and antiglucocorticoid activity
Botella et al. assessed the in vitro glucocorticoid activity of NOMAC and other synthetic steroids relative to a known glucocorticoid receptor (GR) agonist (dexamethasone) and found that NOMAC had very little interaction with rat liver or kidney GR. NOMAC incubated with rat liver GR for 2 hours had a half maximal inhibitory concentration (IC50) of 167 ± 21 nmol/L (10.3%) relative to dexamethasone (IC50, 17.2 ± 3.8 nmol/L). Although the IC50 of dexamethasone was unchanged after 24 hours, the IC50 of NOMAC increased to 1493 ± 807 nmol/L (1%). These results demonstrate that NOMAC has less affinity for rat liver GR over time. These results suggest a low association and faster dissociation to rat GR of NOMAC compared with dexamethasone. However, this effect was not observed when testing the glucocorticoid effect of NOMAC on hGR.
The effect of NOMAC and comparator progestogens on the pituitary-adrenal axis was assessed in OVX rats by measuring plasma corticosterone and the weight of the adrenal glands. Ten days post-ovariectomy, 30-day-old Sprague–Dawley OVX rats (n = 8-28 rats/group) received oral vehicle (no progestogen), progesterone (10 mg/rat/day), NOMAC (0.3-3.0 mg/rat/day), or MPA (0.1-3.0 mg/rat/day) for 14 days. A fifth non-OVX group received oral vehicle. On Day 15, plasma corticosterone was determined in 5 rats/group and, in another 5 rats/group, adrenal glands were removed and examined for morphological changes. The adrenal glands were removed and weighed in the remaining rats. Comparisons among groups were made using ANOVA methods.
Effect of progesterone, NOMAC, and MPA on the pituitary-adrenal axis in OVX rats
Adrenal weight (mg)
Control (No OVX)
46.59 ± 1.51*
53.32 ± 1.63
39.98 ± 2.15*
58.38 ± 3.53
60.28 ± 1.89*
59.43 ± 2.03*
47.28 ± 2.66*
37.35 ± 1.77*
27.58 ± 1.15*
20.86 ± 1.14*
To directly test for anti-inflammatory activity, the effects of NOMAC, hydrocortisone, and MPA on cotton/wool-stimulated inflammatory responses in rats were investigated. Sprague–Dawley male rats (weight, 80-100 g; n = 8 per group) were placed on one of the following once-daily oral dosing regimens for 10 days: vehicle (negative control), NOMAC (2.5-10 mg/kg), or MPA (2.5-10 mg/kg). On Day 7, a cotton/wool pellet was implanted subcutaneously in all rats to induce an inflammatory response. On Days 7-10, 2 groups of vehicle-treated rats received twice-daily, fixed oral doses of the glucocorticoid hydrocortisone (10 or 80 mg/kg). On Day 10, rats in all groups were sacrificed, and the adrenal glands and thymus were removed and weighed. Granulomas that had formed around the cotton/wool pellets were removed, dried for 24 hours in an oven (80°C), and weighed. In one rat per group, implantation zones around the pellet, thymus, and adrenals were removed, placed in Bouin’s fixative for 48 hours, processed, and examined with histopathological methods for signs of vascular, cellular, and fibrous reactions (indicative of inflammation).
Effect of hydrocortisone, NOMAC, and MPA on inflammatory response
Adrenal weight (mg)
Thymus weight (mg)
Granuloma weight (mg)
38.8 ± 1.4
607 ± 34
29.7 ± 1.5
28.6 ± 1.1*
355 ± 42*
24.6 ± 1.4*
25.0 ± 0.9*
139 ± 15*
22.0 ± 1.4*
36.2 ± 2.1
614 ± 43
23.3 ± 1.4*
35.8 ± 1.7
586 ± 28
27.1 ± 2.5
36.7 ± 1.0
576 ± 46
26.4 ± 1.6
32.4 ± 1.0*
636 ± 25
25.4 ± 1.7
30.4 ± 1.5*
624 ± 42
25.8 ± 2.1
24.2 ± 1.4*
512 ± 20*
24.6 ± 1.9*
Granulomas indicative of inflammation formed around the cotton/wool pellet in all groups. Hydrocortisone (10 and 80 mg/kg) inhibited the growth of granuloma tissue around the cotton/wool implants by 18% and 27%, respectively. In rats that received NOMAC, dose-dependent inhibition of inflammation was not observed. At the lowest dose (2.5 mg/kg), NOMAC inhibited the development of granuloma tissue significantly (P<0.01), but larger doses of NOMAC (≥5.0 mg/kg) had no significant effect on granuloma tissue weight (P≥0.05). The highest dose of MPA (10 mg/kg) significantly reduced (P<0.05) granuloma tissue weight. Although a low dose of NOMAC (2.5 mg/kg) inhibited granuloma formation, histopathology did not reveal signs indicative of anti-inflammatory activity or adrenal atrophy. In summary, these data suggest that NOMAC does not inhibit the pituitary-adrenal axis and has minimal (if any) direct anti-inflammatory or apparent glucocorticoid activity.
Central nervous system
Ovariectomy significantly reduces circulating as well as brain concentrations of hormonal factors known to effect mood, such as allopregnanolone and beta-endorphin [33, 34]. In female OVX Wistar rats, oral NOMAC (0.5 and 1 mg/kg/day) significantly increased allopregnanolone in the hippocampus, but not in other areas of the brain . NOMAC (1 mg/kg/day) also increased beta-endorphin in the hippocampus and NOMAC (0.5 and 1 mg/kg/day) increased beta-endorphin in the hypothalamus. In the same study, estradiol valerate (0.05 mg/kg/day) alone increased allopregnanolone and beta-endorphin in OVX rats. Combining 1 mg/kg/day NOMAC and estradiol valerate increased allopregnanolone concentrations to values higher than with either drug alone. Coadminstra-tion of NOMAC (1 mg/day) and estradiol valerate increased beta-endorphin values significantly in hippocampus, frontal, parietal, and hypothalamic areas of the brain, as well as plasma to values higher than with either drug alone, and to levels similar to those observed in unoperated controls. Coadministration of lower doses of NOMAC (0.05, 0.1, 0.2, 0.5 mg/kg/day) and estradiol valerate did not augment brain concentrations of beta-endorphin. The effect of NOMAC in this OVX rat model system to influence allopregnanolone and beta-endorphin was different from other progestogens, including progesterone, DRSP, MPA, and dydrogesterone [33–35].
Mineralocorticoid and antimineralocorticoid activity
Mineralocorticoids (including aldosterone) deserve special attention because they have been shown to interact with progesterone to alter renal function in rats . In the presence of mineralocorticoid hormones, progesterone increases the loss of sodium and chloride in urine and inhibits aldosterone binding to mineralocorticoid receptors (MRs) . Progesterone [36–38] and NOMAC  also inhibit 3H]-aldosterone binding to rat kidney MRs. In contrast, derivatives of 17alpha-hydroxyprogesterone (such as MPA and MAC) do not inhibit the binding of 3H]-aldosterone to rat kidney MRs .
In 3 previously unpublished studies, the antimineralocorticoid activity of oral NOMAC was assessed in OVX rats using a method similar to one described previously . In all 3 studies, Wistar rats underwent bilateral ovariectomy to decrease the concentration of endogenous progesterone (antimineralocorticoid). After a 1-week recovery period, urine was collected overnight for baseline assessment (sampling time: t0) of urinary sodium [Na+ and potassium [K+. On Day 8, rats received a placebo (oral vehicle), NOMAC, or reference compound (spironolactone or DRSP) in the morning and urine was collected overnight (sampling time: t1). On Days 9 and 10, rats received the same compound they received during the morning of Day 8. Urine was also collected during the night of Day 10 (sampling time: t3).
Effects on carbohydrate and lipid metabolism
Effect of 21 days treatment with 10 mg/day NOMAC on mean metabolic parameters in OVX rats compared with intact and OVX controls
Alkaline phosphatase (U/L)
Total cholesterol (g/L)
HDL cholesterol (g/L)
In summary, NOMAC administration had little effect on carbohydrate and lipid metabolism in rats. Moreover, NOMAC and E2 administration to nonhuman primates did not alter total cholesterol, HDL, or plasma triglycerides [44, 45]. These data have been confirmed in clinical studies .
Effects on bone
Effect of NOMAC on osteodensitometry (DEXA) measurements of L1 to L5 of the lumbar rachis
DEXA measurements (%)
104.8 ± 1.4
105.5 ± 2.5
105.9 ± 1.5
108.0 ± 1.4
% treatment of intact control
94.4 ± 2.3
95.5 ± 1.7
97.0 ± 2.8
95.1 ± 2.7
% treatment of intact control
E2 (1 μg/kg/day)†
98.2 ± 0.7
100.8 ± 1.4
103.6 ± 1.7
102.8 ± 1.8
% treatment of OVX control
NOMAC (1 mg/kg/day)†
92.7 ± 0.8
93.4 ± 0.5
92.2 ± 1.1
93.2 ± 2.3
% treatment of OVX control
E2 (1 μg/kg/day) + NOMAC (1 mg/kg/day)†
98.7 ± 1.1
97.5 ± 1.9
102.0 ± 1.0
101.5 ± 1.1
% treatment of OVX control
Effect on endothelial function and the cardiovascular system
The effects of progestogens on endothelial function are complex, partially mediated by progestogen binding to the androgen receptor (AR), ER, GR, or MR . However, the effect of E2 on endothelial function is unequivocal: E2 can enhance the production of endothelial nitric oxide synthase (eNOS), increasing the release of nitric oxide, which can relax vascular smooth muscle, inhibit platelet aggregation, and inhibit the progression of atherosclerosis . In contrast to the effects of E2, the effect of progestogens on endothelium-dependent vasodilation and antiplatelet activity are less well understood. It has been proposed that progestogens with non-androgenic activity and antimineralocorticoid properties are not deleterious to cardiovascular health, especially when used in combination with E2 . NOMAC, which displays moderate anti-androgenic activity, can stimulate nitric oxide synthesis, eNOS activity, and eNOS expression in human endothelial cells derived from human umbilical veins  and does not impair estrogen-dependent induction of eNOS . In a comparative study, MPA and progesterone markedly decreased eNOS mRNA and protein in endothelial cells, whereas LNG and NOMAC had minimal effects on eNOS .
NOMAC appears to have a neutral effect on cardiovascular function. Intramuscular administration of NOMAC (0.5 or 2.5 mg/kg) over 4 hours in halothane anesthetized male beagle dogs (n = 5 per group) did not produce statistically significant differences in blood pressure, heart rate, femoral blood flow and resistance, carotid flow and resistance, cardiac flow, total peripheral resistance, or maximal ventricular performance when compared with a vehicle-treated control group (data on file with MSD). In female Cynomolgus monkeys, supramaximal single oral doses of NOMAC (5, 20, and 80 mg/kg) did not alter hemodynamics (heart rate and arterial blood pressure) or cardiac electrophysiologic parameters (PQ, QRS, QT, and heart rate-corrected QT intervals) over a 6-hour period (data on file with MSD). These doses were much higher than the ID50 reported for ovulation inhibition (0.14 mg/kg) in the same species . Taken together, these studies suggested that NOMAC did not affect parameters of cardiovascular function in dogs and nonhuman primates. NOMAC may have an inhibitory effect on prostaglandin-induced contractions of uterine smooth muscle , but any effect on prostanoid-mediated effects in the vasculature is not known.
Pharmacokinetics and metabolism
NOMAC pharmacokinetics have been investigated most extensively in humans [53, 54]. In women, oral administration of 2.5 mg NOMAC per day results in rapid absorption with a time to maximal concentration of approximately 1.5 hours. Elimination half-life is approximately 46 hours and steady state is reached after 5 days of dosing.
Nomegestrol acetate is metabolized by hepatic cytochrome P450 (CYP) system enzymes, including CYP3A3, CYP3A4, and CYP2A6 into metabolites with little or no effect on progesterone receptor activity . As such, there is a possibility for drug interactions when combined with inducers or inhibitors of the CYP system, such as rifampicin or ketoconazole. Excretion is via the urine and feces .
NOMAC, a highly selective contraceptive progestogen derived from 19-nor-progesterone, is a full PR agonist without significant agonistic or antagonistic ER activity. NOMAC binds with strong affinity to PR in hormone-sensitive cells derived from rat, rabbit, or human. It possesses strong antigonadotropic activity (dose-dependent inhibition of ovulation in rats and nonhuman primates) and has indirect, PR-mediated anti-estrogenic effects. In addition, NOMAC does not exhibit androgenic activity and has moderate anti-androgenic activity in rats. It is also devoid of glucocorticoid and antimineralocorticoid activity and does not appear to adversely affect lipid or carbohydrate metabolism, BMD, endothelial function, or hemodynamic parameters in selected animal models. NOMAC combined with E2 has been developed as a new monophasic oral contraceptive [5–10].
HvD participated as an investigator in a number of the described studies done by Organon, Schering-Plough, and most recently, Merck. He made substantial contributions to analysis and interpretation of data, drafting the manuscript, revising critically for intellectual content, and approved the final manuscript.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA, provided financial support for the studies described.
- B max :
Maximum concentration of binding sites
Bone mineral density
Chinese hamster ovary
Combined oral contraceptives
Dual-energy X-ray absorptiometry
Endothelial nitric oxide synthase
Human androgen receptor
High-density lipoprotein cholesterol
Human estrogen receptor α
Human estrogen receptor β
Human glucocorticoid receptor
Human mineralocorticoid receptor
Human progesterone receptor B
Half maximal inhibitory concentration
50% inhibition dose
- k d :
- k −1 :
Dissociation rate constant
Parametrial adipose tissue
Relative binding affinity
The research work described in the paper was performed by scientists at either Theramex (now Teva) or Organon and/or Schering-Plough, (now Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA). Medical writing and editorial assistance was provided by Alex Loeb, PhD, CMPP, and A. Peter Morello III, PhD, CMPP, of Evidence Scientific Solutions, Philadelphia, PA. This assistance was funded by Merck & Co., Inc.
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