NPASS Compound

Natural Product: NPC471744

Natural Product ID	NPC471744
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-Acetyl Catechin
IUPAC Name	[(2S,3S)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-2,3-dihydrochromen-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3109442
PubChem CID	76313957
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones [CHEMONTID:0001362] Flavanonols

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 39 41 0 0 0 0 0 0 0 0999 V2000 2.0561 -3.3178 1.6500 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3517 -2.7314 0.4606 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6094 -3.1498 -0.6967 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4107 -1.7253 0.6118 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2183 -1.2099 -0.5139 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0176 0.2677 -0.7044 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8557 1.0401 0.1690 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2252 0.8164 0.1833 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1342 1.8355 0.4958 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4663 1.5689 0.4970 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9093 0.2947 0.1898 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0054 -0.7005 -0.1163 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6477 -0.4599 -0.1256 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6820 -1.5034 -0.4474 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1077 -2.6580 -0.6682 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5133 -1.9560 -0.4153 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3540 2.6038 0.8125 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3587 0.7093 -0.4645 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2031 0.9527 -1.5241 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5067 1.3708 -1.3316 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0116 1.5606 -0.0559 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1714 1.3185 1.0042 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8742 0.9021 0.7951 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3247 1.9807 0.0922 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2959 1.5959 -2.4261 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5073 -3.1339 2.5782 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1635 -4.4134 1.4629 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0571 -2.8393 1.6760 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1556 -1.7180 -1.4209 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3803 0.5119 -1.7304 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7128 2.8076 0.7258 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9596 0.1156 0.1988 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5750 -2.1987 -1.4023 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1933 3.0393 1.7290 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8783 0.8260 -2.5459 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5321 1.4561 2.0008 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2579 0.7267 1.6670 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5886 2.9271 0.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6430 2.4876 -2.7211 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 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 12 16 1 0 10 17 1 0 6 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 21 24 1 0 20 25 1 0 14 5 1 0 13 8 1 0 23 18 1 0 1 26 1 0 1 27 1 0 1 28 1 0 5 29 1 0 6 30 1 0 9 31 1 0 11 32 1 0 16 33 1 0 17 34 1 0 19 35 1 0 22 36 1 0 23 37 1 0 24 38 1 0 25 39 1 0 M END

Standard InCHIKey	NPWRSXJQDKRXOR-DLBZAZTESA-N
Standard InCHI	InChI=1S/C17H14O8/c1-7(18)24-17-15(23)14-12(22)5-9(19)6-13(14)25-16(17)8-2-3-10(20)11(21)4-8/h2-6,16-17,19-22H,1H3/t16-,17+/m0/s1
SMILES	CC(=O)OC1C(OC2=CC(=CC(=C2C1=O)O)O)C3=CC(=C(C=C3)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	346.07	Volume:	326.149 ? Van der Waals volume.
Dense:	1.061	LogP:	1.386 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.551 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.603 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	19.0
TPSA:	133.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.477	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.453	Fsp³:	0.176
MCE-18:	64.0 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.581	Fluc inhibitor:	0.283 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.437 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.277 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.611	Promiscuous compounds:	0.054

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.505	MDCK Permeability:	-4.82
Pgp-inhibitor:	0.212	Pgp-substrate:	0.097
PAMPA:	0.495 ? 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):	0.212
20% Bioavailability (F20%):	0.937	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.811
Plasma Protein Binding (PPB):	93.017%	Volume Distribution (VD):	-0.606
Fu:	5.919% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.516
BSEP inhibitor:	0.079

ADMET: Metabolism

CYP1A2-inhibitor:	0.941	CYP1A2-substrate:	0.009
CYP2C19-inhibitor:	0.014	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.666	CYP2C9-substrate:	0.073
CYP2D6-inhibitor:	0.454	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.023
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.98
HLM stability:	0.568 ? 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):

10.438

Half-life (T1/2):

1.356

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.593
Human Hepatotoxicity (H-HT):	0.586	Drug-induced Liver Injury (DILI):	0.582
AMES Toxicity:	0.725	Rat Oral Acute Toxicity:	0.576
Maximum Recommended Daily Dose:	0.708	Skin Sensitization:	0.951
Carcinogencity:	0.491	Eye Corrosion:	0.006
Eye Irritation:	0.946	Respiratory Toxicity:	0.337
Drug-induced Neurotoxicity:	0.044	Ototoxicity:	0.621
Hematotoxicity:	0.071	Drug-induced Nephrotoxicity:	0.142
Genotoxicity:	0.989	RPMI-8226 Immunitoxicity:	0.037
A549 Cytotoxicity:	0.749	Hek293 Cytotoxicity:	0.697
BCF:	0.925 ? 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:	3.484 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.517 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.046 ? 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
NPO33509	byrsonima coccolobifolia	Species	Malpighiaceae	Eukaryota	leaves and stems	cerrado at the Federal University of So Carlos (UFSCar), So Carlos, SP, Brazil	2011-Jul	PMID[24521209]

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
NPT1662	Individual protein	Arginase	Leishmania amazonensis	IC50	=	3700.0	nM	PMID[19687243]

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 NPC471744 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	14757
0.1-0.2	29157
0.2-0.3	5194
0.3-0.4	581
0.4-0.5	128
0.5-0.6	16
0.6-0.7	16
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
0.7885	Intermediate Similarity	NPC609747
0.7273	Intermediate Similarity	NPC112418
0.661	Remote Similarity	NPC295650
0.6562	Remote Similarity	NPC270578
0.6562	Remote Similarity	NPC160156
0.6562	Remote Similarity	NPC250963
0.6562	Remote Similarity	NPC274256
0.6562	Remote Similarity	NPC92565
0.6562	Remote Similarity	NPC109582
0.6562	Remote Similarity	NPC291220
0.6562	Remote Similarity	NPC52382
0.6491	Remote Similarity	NPC471515
0.614	Remote Similarity	NPC36835
0.614	Remote Similarity	NPC246162
0.614	Remote Similarity	NPC9743
0.614	Remote Similarity	NPC260491
0.614	Remote Similarity	NPC61506
0.614	Remote Similarity	NPC240476
0.5965	Remote Similarity	NPC471500
0.5965	Remote Similarity	NPC321011
0.5965	Remote Similarity	NPC294852
0.5965	Remote Similarity	NPC188679
0.5833	Remote Similarity	NPC471745
0.5672	Remote Similarity	NPC153342
0.5345	Remote Similarity	NPC62290
0.5345	Remote Similarity	NPC142731
0.5345	Remote Similarity	NPC326506
0.5294	Remote Similarity	NPC482602
0.5085	Remote Similarity	NPC261619
0.5085	Remote Similarity	NPC61477
0.5085	Remote Similarity	NPC78770
0.5085	Remote Similarity	NPC219876
0.5085	Remote Similarity	NPC126029
0.5085	Remote Similarity	NPC15658

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471744 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3852
0.1-0.2	5157
0.2-0.3	128
0.3-0.4	4
0.4-0.5	7
0.5-0.6	2
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
0.5085	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.5085	Remote Similarity	NPD1613	Phase 4

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