What Is The Chemical Structure Of Enclomiphene?

Disclaimer. Enclomiphene is supplied strictly as a laboratory research material. It is not for human consumption of any kind, and nothing below is guidance on administering it to a person or an animal. The statements on this page have not been evaluated by the US Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease. Handling is restricted to trained professionals working under applicable regulations.

The chemical structure of enclomiphene is a triphenylethylene skeleton: one carbon-carbon double bond carrying three benzene rings and a single chlorine atom, with a 2-(diethylamino)ethoxy side chain attached at the para position of one of those rings. The molecular formula is C26H28ClNO and the molecular weight is 405.96 g/mol. Enclomiphene is the (E)-geometric isomer of clomiphene. Its counterpart, zuclomiphene, is the (Z)-isomer and has exactly the same formula and exactly the same mass. The geometry across that one double bond is the whole difference between them, and it is the reason the two materials behave differently in receptor assays.

That single structural detail is what this page is about, because it is also the detail most likely to get lost between a supplier's label and a researcher's notebook.

What Is Enclomiphene?

Enclomiphene is the (E)-stereoisomer of clomiphene, a non-steroidal triphenylethylene that acts as an estrogen receptor antagonist in receptor binding work. It carries CAS number 15690-57-0, PubChem CID 1548953, and the IUPAC name 2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine. Clomiphene itself is not a single substance but a mixture of this isomer and its Z counterpart.

The parent material, clomiphene, has its own CAS number (911-45-5) and is sold pharmaceutically as the citrate (50-41-9). What that citrate contains is a mixture. US Food and Drug Administration briefing material prepared for its 2022 Pharmacy Compounding Advisory Committee review states the split as 62% enclomiphene and 38% zuclomiphene, and the NIH substance registry records the same figures. Patent filings describing marketed material give a wider working range, 50% to 70% enclomiphene against 30% to 50% zuclomiphene, depending on the synthetic route. We weight the 62:38 figure higher as the nominal composition because two independent government databases carry it, and we read the patent range as what actually comes off a production line.

The Chemical Structure Of Enclomiphene, Atom By Atom

Walk the molecule from its centre outward and it resolves into four parts.

The ethylene core. A single C=C double bond. This is the hinge the whole identity question turns on, because its two faces cannot rotate past each other at room temperature.

Carbon 1 of that bond carries two aryl groups: an unsubstituted phenyl ring, and a para-substituted phenyl ring.

Carbon 2 carries one unsubstituted phenyl ring and one chlorine atom.

The side chain. Hanging off the para position of that substituted ring is an ether oxygen, then an ethyl bridge, then a tertiary amine bearing two ethyl groups. That is the 2-(diethylamino)ethoxy group, and it is the only basic site in the molecule. It is also why enclomiphene is supplied as a salt rather than a free base in most catalogs.

Three phenyl rings plus one chlorine on a two-carbon alkene is the triphenylethylene class, and it puts enclomiphene in the same structural family as tamoxifen and toremifene.

The identity record for the free base reads as follows. Molecular formula C26H28ClNO. Molecular weight 405.96 g/mol, with an exact monoisotopic mass of 405.1859. CAS number 15690-57-0. PubChem CID 1548953. UNII R6D2UI4FLS. KEGG entry D08910. InChIKey GKIRPKYJQBWNGO-OCEACIFDSA-N. Isomeric SMILES CCN(CC)CCOC1=CC=C(C=C1)C(=C(\Cl)C2=CC=CC=C2)\C3=CC=CC=C3. Elemental composition runs C 76.92%, H 6.95%, Cl 8.73%, N 3.45%, O 3.94%.

One field in that list deserves a second look. Enclomiphene has zero stereocenters. The NIH substance registry classifies it as achiral, with no optical activity, no defined stereocenters, and exactly one E/Z center. People hear "isomer" and reach for chirality, enantiomers, optical rotation. None of that applies here. There is one geometric center and nothing else, which means polarimetry will tell you nothing about which isomer is in the vial.

Why Does The E Configuration Change The Molecule?

The E and Z descriptors record which side of the double bond each substituent sits on, and because that bond cannot rotate, the two arrangements are separate materials with separate properties. In enclomiphene, the chlorine and the diethylaminoethoxy-bearing ring are positioned across from each other in the E arrangement. In zuclomiphene they sit on the same side.

That changes the three-dimensional shape of the molecule, which changes how it sits in the estrogen receptor's ligand-binding pocket. The E isomer behaves as an antagonist in receptor work. The Z isomer shows agonist character in the same assays. Same atoms, same connectivity, same mass, opposite behaviour at the receptor. Published comparisons of the two across estrogen-responsive tissue models have been running since the 1980s.

The geometry also shows up in bulk physical properties, which matters if you are checking a material against a reference. Work by Ernst and colleagues, published in the Journal of Pharmaceutical Sciences in 1976 and still the standard citation for the stereochemistry of these isomers, reports the hydrochloride of the E isomer melting at 149 to 150.5 degrees C and the hydrochloride of the Z isomer at 156.5 to 158 degrees C. That is a gap of 7.5 degrees on the same formula.

Be careful with melting point as a sole check on the citrate, though. Patent filings reviewing the literature note that enclomiphene citrate has been reported at more than one melting point, including 133 to 135 degrees C, so a figure that does not match your reference is not automatically a failed identity test.

Enclomiphene Vs Zuclomiphene: Same Formula, Different Material

Here is the comparison the database pages never put side by side.

Both isomers share a molecular formula of C26H28ClNO and a molecular weight of 405.96 g/mol. Everything that separates them is registry data and geometry.

Enclomiphene is the (E) isomer, commonly labelled trans-clomiphene. Free base CAS 15690-57-0, citrate CAS 7599-79-3, hydrochloride CAS 14158-65-7. PubChem CID 1548953. UNII R6D2UI4FLS. InChIKey GKIRPKYJQBWNGO-OCEACIFDSA-N. It behaves as an antagonist in receptor assays and makes up 62% of clomiphene citrate. Development code RMI-16289.

Zuclomiphene is the (Z) isomer, commonly labelled cis-clomiphene. Free base CAS 15690-55-8, citrate CAS 7619-53-6, hydrochloride CAS 14158-66-8. PubChem CID 1548955. UNII 3JU1DU3652. InChIKey GKIRPKYJQBWNGO-QPLCGJKRSA-N. It shows agonist character in the same assays and makes up 38% of clomiphene citrate. Development code RMI-16312.

Look at the two InChIKeys. The first 14 characters are identical, GKIRPKYJQBWNGO, because that block encodes atomic connectivity and the two isomers are connected the same way. The second block diverges, OCEACIFDSA against QPLCGJKRSA, because that block encodes stereochemistry. For anyone building a specification or a search filter, this is the cleanest single-string discriminator available: match the full InChIKey, never the skeleton block alone.

A caution that trips people up: the citrate salt has a different first block (PYTMYKVIJXPNBD-BTKVJIOYSA-N), because the hash covers every component in the formula unit. Searching a database for the free-base InChIKey will not surface citrate records.

The 1976 Nomenclature Reversal That Still Appears In Catalogs

This is the part worth slowing down for, and it is missing from every page currently ranking.

The cis and trans labels for clomiphene's isomers were assigned backwards in the published literature for roughly 15 years. The original isomers were designated A and B. Isomer A was called trans-clomiphene and isomer B was called cis-clomiphene. That assignment was wrong. Ernst and colleagues corrected it in 1976, and the labels swapped: what had been called trans became cis (zuclomiphene), and what had been called cis became trans (enclomiphene). Patent filings that review this history state the position plainly, that before 1976 the cis stereochemistry was wrongly assigned to the trans isomer of clomiphene.

Two consequences follow, and both are live today.

Literature published before 1976 uses the reversed labels. If you are reading a 1960s or early 1970s paper on clomiphene isomers, the cis and trans designations in it mean the opposite of what they mean now. Cross-reference by isomer letter or by described behaviour, not by the geometric label.

The error has contaminated modern synonym fields. Wikipedia's current zuclomifene entry lists "trans-Clomifene" among its alternative names. ChemicalBook's page for CAS 15690-55-8, which is zuclomiphene, includes "Trans-cloMiphene (encloMiphene)" in its synonym block, and its page for 15690-57-0, which is enclomiphene, includes "Cis-cloMiphene (ZucloMiphene)." One commercial catalog lists both "Transclomiphene" and "Cisclomiphene" as synonyms under the same CAS number. These are not obscure sources. They are pages a researcher lands on from a first-page search.

So the working rule for anyone sourcing or specifying this material: treat cis and trans as commentary. Treat the CAS number, the E or Z stereodescriptor, and the full InChIKey as the identity. Those three have never contradicted each other across the records we checked. The word "trans" has.

Free Base, Citrate, And Hydrochloride: The Salt Changes Every Number

Enclomiphene circulates in three forms, and a concentration calculated against the wrong one will be off by a third.

The free base is C26H28ClNO at 405.96 g/mol, which is 100% enclomiphene by definition. The citrate adds citric acid (C6H8O7, 192.12 g/mol) to give a formula unit of C26H28ClNO.C6H8O7 at 598.08 g/mol, of which 67.9% is enclomiphene base. The hydrochloride adds HCl to give C26H28ClNO.HCl at 442.42 g/mol, of which 91.8% is enclomiphene base.

The citrate figure is the one that bites. Citric acid contributes nearly a third of the salt's total mass. Run the ratio and 405.96 divided by 598.08 gives 0.679. So:

• 100 mg of enclomiphene citrate contains 67.9 mg of enclomiphene base.

• To reach 100 mg of base you need 147.3 mg of the citrate.

• A material labelled "12.5 mg" may mean 12.5 mg of citrate (8.5 mg base) or 12.5 mg of base equivalent (18.4 mg citrate). The label alone does not tell you.

That last ambiguity is not hypothetical. "Base equivalent" and "salt weight" are both in common use across catalogs, often unlabelled. Anyone preparing a solution to a target concentration should confirm which convention a certificate uses before weighing anything, the same arithmetic discipline that applies to any target concentration calculation for a research material.

Any strength quoted in a listing name, including our 25 mg enclomiphene page, should be read alongside the certificate for that batch rather than treated as the specification on its own.

For reference, the citrate carries CAS 7599-79-3, PubChem CID 6420009, UNII J303A6U9Y6, molecular formula C32H36ClNO8, molecular weight 598.08, and a monoisotopic mass of 597.2129.

How Do You Confirm The E Isomer On An Analytical Certificate?

Mass spectrometry alone cannot do it. Both isomers have the same molecular formula, the same nominal mass, and the same exact mass of 405.1859. A mass spectrum will confirm you have clomiphene. It will not tell you which isomer, or in what proportion.

Chromatographic separation is what resolves the question. The two isomers separate on reversed-phase HPLC, and separating clomiphene isomers by HPLC has been established method work since at least the mid-1980s. What that means in practice for a certificate:

• A retention time matched against a known reference standard is the identity check. A retention time with nothing to compare it against is a number, not an identification.

• The chromatogram itself should be present, not just a purity figure. A single peak reported as 99% tells you nothing about whether a second isomer co-eluted or was never looked for at all.

• Peak area for the minor isomer is the figure that distinguishes an isomerically pure material from an enriched mixture. Its absence from a certificate is itself information.

• A batch or lot number and a test date must appear, and they must be traceable to the container in your hand.

For a geometric isomer, the chromatogram matters more than it does for a typical single-species material, for the reason this page keeps circling back to: the mass is not diagnostic. Nordic Chems states that every batch is independently tested by accredited labs for identity, purity, and concentration, that the labs it works with are ISO-certified and cGMP-compliant, and that product labels carry the chemical name, concentration, and structure. Independent third-party results and the rest of the documentation standard sit on our quality control page, and we cover how to read one in our writeup on third-party purity verification.

Where Enclomiphene Sits In The 2026 Regulatory Picture

Enclomiphene has never been approved by the US Food and Drug Administration. Repros Therapeutics developed it under the names Androxal and EnCyzix and took it through Phase III, but it did not reach approval, and PubChem records its maximum clinical trial phase as III across all indications.

Its compounding status has been contested. On 8 June 2022, the FDA's Pharmacy Compounding Advisory Committee reviewed enclomiphene citrate for inclusion on the 503A Bulks List. The agency's own position going in was that it should not be included, and the committee voted against inclusion. The substance currently appears in Category 1, under evaluation, on the FDA's interim list of nominated bulk substances.

In sport, the World Anti-Doping Agency prohibits selective estrogen receptor modulators at all times under section S4 of its Prohibited List, and clomifene is named there directly. That list operates by class as well as by name, so anyone working in an anti-doping context should treat an isomer of a named substance accordingly rather than reading its absence from the list as permission.

None of this changes what enclomiphene is sold as here. It is a research material. It is not for human consumption, the position that governs our enclomiphene listing and every other item we stock, and we explain the reasoning behind research use only labelling separately.

Research Context And Handling Notes

In the literature, enclomiphene appears in receptor pharmacology work on estrogen receptor binding and in analytical method development, where it serves as a reference standard for isomer separation and for method validation against clomiphene. Its structural relationship to other triphenylethylenes makes it a frequent comparator in structure-activity studies of the class.

On handling: the material is light sensitive, and catalog storage guidance across suppliers converges on cool, dry, tightly closed containers kept in an area restricted to qualified personnel. Handle with appropriate PPE and standard laboratory safety practice, and follow applicable regulations for storage, transport, and disposal. Because the cis and trans literature is as tangled as described above, keep the certificate with the container rather than relying on a shelf label.

The chemical structure of enclomiphene is settled chemistry, documented across PubChem, the NIH substance registry, KEGG, and the Protein Data Bank, and it has been settled since 1976. What is not settled is the labelling around it. If you take one thing from this page, take the habit of verifying by CAS number, stereodescriptor, and full InChIKey, and treating every cis or trans label you meet as a claim that needs checking. For anyone cross-referencing a related molecule, our aniracetam structure reference follows the same format.

Disclaimer. All products on this site are for research and development use only. Products are not for human consumption of any kind. The statements made within this website have not been evaluated by the US Food and Drug Administration. The statements and the products of this company are not intended to diagnose, treat, cure, or prevent any disease.

FAQs

What is the chemical structure of enclomiphene? 

Enclomiphene is a triphenylethylene: a carbon-carbon double bond carrying three benzene rings and one chlorine atom, with a 2-(diethylamino)ethoxy side chain at the para position of one ring. Its molecular formula is C26H28ClNO and its molecular weight is 405.96 g/mol. It is the (E)-geometric isomer of clomiphene, registered under CAS number 15690-57-0.

What is the difference between enclomiphene and zuclomiphene? 

They are geometric isomers with identical molecular formulas (C26H28ClNO), identical molecular weights (405.96 g/mol), and different arrangements across the central double bond. Enclomiphene is the E isomer, CAS 15690-57-0. Zuclomiphene is the Z isomer, CAS 15690-55-8. Enclomiphene acts as an estrogen receptor antagonist in receptor assays, while zuclomiphene shows agonist character.

Is enclomiphene the same as clomiphene? 

No. Clomiphene is a mixture of both geometric isomers. US Food and Drug Administration briefing material gives the nominal split as 62% enclomiphene and 38% zuclomiphene, while patent filings describing production material report a working range of 50% to 70% enclomiphene. Enclomiphene is the isolated E isomer.

Does enclomiphene have stereocenters?

No. The NIH substance registry classifies enclomiphene as achiral with zero defined stereocenters, zero optical activity, and exactly one E/Z center. The only stereochemistry in the molecule is the geometry of the double bond, so optical rotation cannot distinguish the isomers.

How much enclomiphene is in enclomiphene citrate? 

Enclomiphene citrate has a molecular weight of 598.08 g/mol against the free base's 405.96 g/mol, so the base accounts for 67.9% of the salt's mass. 100 mg of the citrate contains 67.9 mg of enclomiphene base, and 147.3 mg of the citrate is needed to reach 100 mg of base.

Why do some sources call enclomiphene the cis isomer? 

Because the cis and trans labels for clomiphene's isomers were assigned backwards in the literature until Ernst and colleagues corrected them in 1976. Pre-1976 papers use the reversed labels, and the error still shows up in some database synonym fields and supplier catalogs. Verify identity by CAS number, E or Z descriptor, and full InChIKey rather than by a cis or trans label.

Is enclomiphene approved in the United States? 

No. Enclomiphene has never received US Food and Drug Administration approval. It reached Phase III under development names Androxal and EnCyzix. In June 2022 the FDA's Pharmacy Compounding Advisory Committee voted against adding enclomiphene citrate to the 503A Bulks List. Nordic Chems supplies it strictly as a research material, not for human consumption.