NPASS Compound

Natural Product: NPC148969

Natural Product ID	NPC148969
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl 3-(3,4-Dihydroxyphenyl)Propanoate
IUPAC Name	methyl 3-(3,4-dihydroxyphenyl)propanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3093470
PubChem CID	579668
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0001286] Benzenediols [CHEMONTID:0000135] Catechols

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 26 26 0 0 0 0 0 0 0 0999 V2000 5.1411 -0.0679 -0.1435 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8088 0.0218 -0.6088 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7656 -0.1882 0.3130 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0150 -0.4476 1.5133 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3891 -0.0799 -0.2398 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4452 -0.3386 0.9092 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9740 -0.2612 0.4962 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6879 -1.3470 0.0404 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0101 -1.2506 -0.3390 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6220 0.0021 -0.2482 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9293 1.1057 0.2052 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5965 0.9656 0.5782 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5758 2.3412 0.2818 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9575 0.1675 -0.6164 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2514 -0.8358 0.6618 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5021 0.9169 0.1965 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7605 -0.3529 -1.0417 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2497 -0.7636 -1.0807 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2719 1.0047 -0.5331 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6488 0.4477 1.6711 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7010 -1.3017 1.3944 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2133 -2.3147 -0.0292 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5837 -2.0903 -0.6980 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0772 1.8662 0.9342 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0918 3.1544 -0.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6311 -0.3539 -0.0534 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 3 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 11 13 1 0 10 14 1 0 12 7 1 0 1 15 1 0 1 16 1 0 1 17 1 0 5 18 1 0 5 19 1 0 6 20 1 0 6 21 1 0 8 22 1 0 9 23 1 0 12 24 1 0 13 25 1 0 14 26 1 0 M END

Standard InCHIKey	NTULQOXXTCSEHM-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C10H12O4/c1-14-10(13)5-3-7-2-4-8(11)9(12)6-7/h2,4,6,11-12H,3,5H2,1H3
SMILES	COC(=O)CCc1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	196.07	Volume:	197.575 ? Van der Waals volume.
Dense:	0.992	LogP:	1.473 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.205 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.895 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	7.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.563	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.849	Fsp³:	0.3
MCE-18:	7.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.215	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.09 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.054 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.974	Promiscuous compounds:	0.272

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.792	MDCK Permeability:	-4.59
Pgp-inhibitor:	0.786	Pgp-substrate:	0.064
PAMPA:	0.06 ? 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):	0.077
20% Bioavailability (F20%):	0.893	30% Bioavailability (F30%):	0.982
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.467
Plasma Protein Binding (PPB):	76.443%	Volume Distribution (VD):	-0.364
Fu:	22.494% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.896
OATP1B3 inhibitor:	0.957	BCRP inhibitor:	0.566
BSEP inhibitor:	0.969

ADMET: Metabolism

CYP1A2-inhibitor:	0.399	CYP1A2-substrate:	0.49
CYP2C19-inhibitor:	0.066	CYP2C19-substrate:	0.449
CYP2C9-inhibitor:	0.929	CYP2C9-substrate:	0.013
CYP2D6-inhibitor:	0.743	CYP2D6-substrate:	0.181
CYP3A4-inhibitor:	0.044	CYP3A4-substrate:	0.843
CYP2B6-substrate:	0.041	CYP2C8-inhibitor:	0.999
HLM stability:	0.789 ? 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):

15.292

Half-life (T1/2):

1.494

ADMET: Toxicity

hERG Blockers:	0.099	hERG Blockers (10um):	0.586
Human Hepatotoxicity (H-HT):	0.445	Drug-induced Liver Injury (DILI):	0.154
AMES Toxicity:	0.431	Rat Oral Acute Toxicity:	0.198
Maximum Recommended Daily Dose:	0.394	Skin Sensitization:	0.916
Carcinogencity:	0.637	Eye Corrosion:	0.806
Eye Irritation:	0.989	Respiratory Toxicity:	0.255
Drug-induced Neurotoxicity:	0.128	Ototoxicity:	0.636
Hematotoxicity:	0.2	Drug-induced Nephrotoxicity:	0.49
Genotoxicity:	0.092	RPMI-8226 Immunitoxicity:	0.017
A549 Cytotoxicity:	0.036	Hek293 Cytotoxicity:	0.036
BCF:	0.483 ? 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:	3.0 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.59 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.897 ? 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
NPO8251	Cortex lycii radicis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8251	Cortex lycii radicis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]

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	2
EC50	1
Ratio CC50/IC50	1
CC50	2
ID50	8

Activity Type	# Activity
Cell line	2
Individual protein	1
Others	2
Organism	8
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT725	Individual protein	2-heptyl-4(1H)-quinolone synthase PqsD	Pseudomonas aeruginosa	IC50	=	23000.0	nM	PMID[25437621]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT616	Cell line	MDCK	Canis lupus familiaris	CC50	>	237980.0	nM	PMID[24803363]
NPT189	Cell line	Vero	Chlorocebus aethiops	CC50	=	100.0	ug.mL-1	PMID[26260341]
NPT4194	Organism	Human adenovirus type 2	Human adenovirus 2	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT3148	Organism	Cytomegalovirus	Cytomegalovirus	ID50	=	100.0	ug ml-1	PMID[26260341]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	23780.0	nM	PMID[24803363]
NPT4691	Organism	Human poliovirus 1 strain Sabin	Human poliovirus 1 strain Sabin	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT3119	Organism	Human coxsackievirus B3	Human coxsackievirus B3	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT4692	Organism	Human echovirus 9	Human echovirus 9	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT190	Organism	Human herpesvirus 1	Human herpesvirus 1	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT1141	Organism	Human herpesvirus 2	Human herpesvirus 2	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT1	Others	Radical scavenging activity	n.a.	EC50	=	161.9	ug.mL-1	PMID[24216089]
NPT4693	Organism	Human adenovirus type 5	Human adenovirus 5	ID50	>	100.0	ug ml-1	PMID[26260341]
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	>	10.01	n.a.	PMID[24803363]

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 NPC148969 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	9725
0.1-0.2	33485
0.2-0.3	6064
0.3-0.4	500
0.4-0.5	69
0.5-0.6	9
0.6-0.7	1
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
0.7179	Intermediate Similarity	NPC472271
0.6053	Remote Similarity	NPC163158
0.5952	Remote Similarity	NPC177291
0.5581	Remote Similarity	NPC70084
0.5476	Remote Similarity	NPC322332
0.5455	Remote Similarity	NPC75039
0.5455	Remote Similarity	NPC98305
0.5405	Remote Similarity	NPC110764
0.525	Remote Similarity	NPC264558
0.5116	Remote Similarity	NPC61062
0.5106	Remote Similarity	NPC86198

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC148969 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2526
0.1-0.2	6321
0.2-0.3	273
0.3-0.4	19
0.4-0.5	9
0.5-0.6	1
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
0.575	Remote Similarity	NPD259	Phase 2

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