NPASS Compound

Natural Product: NPC67349

Natural Product ID	NPC67349
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cimicifugic Acid M
IUPAC Name	(2R,3S)-2-benzyl-3-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-2-hydroxybutanedioic acid
Synonyms	Cimicifugic Acid M
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1096937
PubChem CID	46210733
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 47 48 0 0 0 0 0 0 0 0999 V2000 0.6550 -1.2363 2.8107 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9842 -1.0364 1.6282 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0807 -1.2302 0.6151 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2433 -1.6700 1.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1742 -0.5697 0.5455 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9713 -0.4422 -0.9263 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2132 -1.4024 -1.7023 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5116 0.7459 -1.4453 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6175 -0.8580 0.8795 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4254 0.2989 0.3993 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9630 0.3373 -0.8644 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7150 1.4194 -1.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9203 2.4853 -0.4396 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3899 2.4555 0.8175 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6449 1.3681 1.2385 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8141 0.6409 1.1699 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5748 -2.9185 0.2852 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6351 -3.5452 0.4750 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6746 -3.4239 -0.6391 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3679 -0.5889 1.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8059 -0.3527 0.1561 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1515 0.0898 -0.1815 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4963 0.3054 -1.4962 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7651 0.7281 -1.8796 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7121 0.9395 -0.9149 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4109 0.7363 0.4117 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1302 0.3128 0.7607 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4098 0.9662 1.3456 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9789 1.3595 -1.2734 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3242 -1.7867 2.1017 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6975 1.0375 -2.4080 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9540 -1.7276 0.2658 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7334 -1.0517 1.9492 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7932 -0.4949 -1.5165 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1295 1.4283 -2.3103 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5161 3.3181 -0.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5428 3.2753 1.4989 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2281 1.3550 2.2400 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1823 1.3716 0.6171 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8995 -4.1211 -1.3296 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0478 -0.4483 2.1974 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0872 -0.5079 -0.6390 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7776 0.1486 -2.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0037 0.8889 -2.9282 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9364 0.1659 1.8081 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8998 0.1711 1.7534 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7875 1.0634 -0.7078 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 5 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 5 16 1 1 4 17 1 0 17 18 2 0 17 19 1 0 2 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 25 29 1 0 15 10 1 0 27 22 1 0 4 30 1 1 8 31 1 0 9 32 1 0 9 33 1 0 11 34 1 0 12 35 1 0 13 36 1 0 14 37 1 0 15 38 1 0 16 39 1 0 19 40 1 0 20 41 1 0 21 42 1 0 23 43 1 0 24 44 1 0 27 45 1 0 28 46 1 0 29 47 1 0 M END

Standard InCHIKey	RHQXHDXIEARXSC-DTLVDHMJSA-N
Standard InCHI	InChI=1S/C20H18O9/c21-14-8-6-12(10-15(14)22)7-9-16(23)29-17(18(24)25)20(28,19(26)27)11-13-4-2-1-3-5-13/h1-10,17,21-22,28H,11H2,(H,24,25)(H,26,27)/b9-7+/t17-,20-/m1/s1
SMILES	O=C(O[C@@H]([C@@](C(=O)O)(Cc1ccccc1)O)C(=O)O)/C=C/c1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO30451	Cimicifuga simplex	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[17503850]
NPO33345	cimicifuga japonica	Species	Ranunculaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[20184336]
NPO30451	Cimicifuga simplex	n.a.	n.a.	n.a.	aerial parts	n.a.	n.a.	PMID[20184336]
NPO30451	Cimicifuga simplex	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30451	Cimicifuga simplex	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO30451	Cimicifuga simplex	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT42	Individual protein	Hyaluronidase-1	Homo sapiens	IC50	=	173000.0	nM	DOI[10.1039/C4MD00257A]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC67349 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	12134
0.1-0.2	33585
0.2-0.3	3725
0.3-0.4	312
0.4-0.5	68
0.5-0.6	11
0.6-0.7	18
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8596	High Similarity	NPC279676
0.8571	High Similarity	NPC179505
0.7667	Intermediate Similarity	NPC156709
0.7586	Intermediate Similarity	NPC108553
0.7077	Intermediate Similarity	NPC221383
0.6866	Remote Similarity	NPC283081
0.6818	Remote Similarity	NPC258671
0.6716	Remote Similarity	NPC143892
0.6716	Remote Similarity	NPC299090
0.6716	Remote Similarity	NPC246566
0.6545	Remote Similarity	NPC217052
0.6545	Remote Similarity	NPC329344
0.6545	Remote Similarity	NPC237506
0.6545	Remote Similarity	NPC32626
0.6441	Remote Similarity	NPC251407
0.6441	Remote Similarity	NPC168653
0.6324	Remote Similarity	NPC95498
0.6324	Remote Similarity	NPC304956
0.623	Remote Similarity	NPC18074
0.623	Remote Similarity	NPC5419
0.623	Remote Similarity	NPC25581
0.623	Remote Similarity	NPC61
0.6	Remote Similarity	NPC132921
0.5634	Remote Similarity	NPC53884
0.5538	Remote Similarity	NPC198388
0.5507	Remote Similarity	NPC289690
0.541	Remote Similarity	NPC263386
0.541	Remote Similarity	NPC141791
0.5303	Remote Similarity	NPC475695
0.5224	Remote Similarity	NPC13818
0.5224	Remote Similarity	NPC219428
0.5172	Remote Similarity	NPC44507
0.5143	Remote Similarity	NPC477333
0.5075	Remote Similarity	NPC229264

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC67349 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2322
0.1-0.2	6258
0.2-0.3	550
0.3-0.4	17
0.4-0.5	3
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data