NPASS Compound

Natural Product: NPC289690

Natural Product ID	NPC289690
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Clinopodic Acid B
IUPAC Name	(2R)-2-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-3-(4-hydroxy-3-methoxyphenyl)propanoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1080778
PubChem CID	44254692
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 45 46 0 0 0 0 0 0 0 0999 V2000 -6.0582 0.6327 2.3394 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4190 0.1850 1.0504 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5070 -0.2730 0.1233 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1541 -0.3313 0.3835 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2521 -0.8007 -0.5766 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7767 -1.1978 -1.7812 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1436 -1.1453 -2.0614 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0196 -0.6795 -1.1032 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3914 -0.6120 -1.3454 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8124 -0.8641 -0.2570 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0679 0.4192 -0.5216 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1994 0.7506 -1.9497 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2817 0.9850 -2.5485 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0562 0.8181 -2.7269 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3109 0.2878 -0.2318 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9636 1.1034 0.6780 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2659 1.9790 1.2436 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3999 0.9498 0.9650 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1261 0.0277 0.3668 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5390 -0.2106 0.5724 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2929 0.5314 1.4473 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6623 0.2725 1.6219 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2625 -0.7351 0.9113 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5233 -1.4873 0.0318 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1825 -1.2125 -0.1205 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1645 -2.4989 -0.6703 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6162 -0.9930 1.0822 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2151 0.0588 2.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9039 0.5664 3.0525 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7394 1.6925 2.2953 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7608 -0.0092 1.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1385 -1.5797 -2.5657 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5048 -1.4719 -3.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0512 -0.8727 -0.6278 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3548 -1.6977 -0.8405 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6971 -1.1891 0.8164 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4616 1.2600 0.1028 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0662 1.0200 -3.7185 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9000 1.5905 1.6760 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5764 -0.5993 -0.3468 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8622 1.3300 2.0238 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2071 0.8908 2.3264 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6366 -1.8314 -0.8259 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2741 -2.3378 -1.6819 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2667 -1.0113 0.2922 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 5 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 11 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 23 27 1 0 8 3 1 0 25 20 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 0 7 33 1 0 9 34 1 0 10 35 1 0 10 36 1 0 11 37 1 1 14 38 1 0 18 39 1 0 19 40 1 0 21 41 1 0 22 42 1 0 25 43 1 0 26 44 1 0 27 45 1 0 M END

Standard InCHIKey	NFSDQICEPLDULQ-BBOMDTFKSA-N
Standard InCHI	InChI=1S/C19H18O8/c1-26-16-9-12(3-6-14(16)21)10-17(19(24)25)27-18(23)7-4-11-2-5-13(20)15(22)8-11/h2-9,17,20-22H,10H2,1H3,(H,24,25)/b7-4+/t17-/m1/s1
SMILES	COc1cc(ccc1O)C[C@H](C(=O)O)OC(=O)/C=C/c1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.1	Volume:	366.661 ? Van der Waals volume.
Dense:	1.02	LogP:	1.834 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.939 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.249 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	15.0
TPSA:	133.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.329	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.834	Fsp³:	0.158
MCE-18:	30.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.754	Fluc inhibitor:	0.995 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.049 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.428 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.538	Promiscuous compounds:	0.376

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.155	MDCK Permeability:	-5.107
Pgp-inhibitor:	0.0	Pgp-substrate:	0.012
PAMPA:	0.969 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.946	30% Bioavailability (F30%):	0.923
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.403
Plasma Protein Binding (PPB):	81.874%	Volume Distribution (VD):	-0.389
Fu:	12.022% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.235

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.921	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.006
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.301
HLM stability:	0.014 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

7.695

Half-life (T1/2):

1.757

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.173
Human Hepatotoxicity (H-HT):	0.543	Drug-induced Liver Injury (DILI):	0.894
AMES Toxicity:	0.449	Rat Oral Acute Toxicity:	0.205
Maximum Recommended Daily Dose:	0.522	Skin Sensitization:	0.999
Carcinogencity:	0.12	Eye Corrosion:	0.053
Eye Irritation:	0.939	Respiratory Toxicity:	0.139
Drug-induced Neurotoxicity:	0.064	Ototoxicity:	0.73
Hematotoxicity:	0.098	Drug-induced Nephrotoxicity:	0.716
Genotoxicity:	0.929	RPMI-8226 Immunitoxicity:	0.035
A549 Cytotoxicity:	0.255	Hek293 Cytotoxicity:	0.096
BCF:	0.624 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.406 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.599 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.236 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO13475.1	Clinopodium chinense	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[19711986]
NPO13475.1	Clinopodium chinense	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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
NPT40	Individual protein	72 kDa type IV collagenase	Rattus norvegicus	IC50	>	100000.0	nM	PMID[19114678]

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 NPC289690 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	17630
0.1-0.2	26503
0.2-0.3	4737
0.3-0.4	791
0.4-0.5	151
0.5-0.6	23
0.6-0.7	8
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	Natural Product ID
0.7857	Intermediate Similarity	NPC18074
0.7857	Intermediate Similarity	NPC5419
0.7857	Intermediate Similarity	NPC25581
0.7857	Intermediate Similarity	NPC61
0.7183	Intermediate Similarity	NPC300329
0.7164	Intermediate Similarity	NPC160378
0.7	Intermediate Similarity	NPC198388
0.6765	Remote Similarity	NPC283081
0.6429	Remote Similarity	NPC217052
0.6429	Remote Similarity	NPC329344
0.6429	Remote Similarity	NPC237506
0.6429	Remote Similarity	NPC32626
0.6301	Remote Similarity	NPC173729
0.6176	Remote Similarity	NPC38473
0.6	Remote Similarity	NPC221383
0.5915	Remote Similarity	NPC246566
0.5909	Remote Similarity	NPC179505
0.5902	Remote Similarity	NPC132921
0.5806	Remote Similarity	NPC251407
0.5806	Remote Similarity	NPC168653
0.5735	Remote Similarity	NPC279676
0.5694	Remote Similarity	NPC143892
0.5694	Remote Similarity	NPC299090
0.5584	Remote Similarity	NPC272750
0.5556	Remote Similarity	NPC258671
0.5507	Remote Similarity	NPC67349
0.5455	Remote Similarity	NPC41494
0.5455	Remote Similarity	NPC186100
0.5455	Remote Similarity	NPC189197
0.5345	Remote Similarity	NPC107588
0.5345	Remote Similarity	NPC137537
0.5342	Remote Similarity	NPC95498
0.5286	Remote Similarity	NPC156709
0.5147	Remote Similarity	NPC110699
0.5147	Remote Similarity	NPC106055
0.5135	Remote Similarity	NPC304956
0.5077	Remote Similarity	NPC488563
0.5075	Remote Similarity	NPC213552

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC289690 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2764
0.1-0.2	6003
0.2-0.3	370
0.3-0.4	10
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