NPASS Compound

Natural Product: NPC538289

Natural Product ID	NPC538289
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-(3-hydroxy-3-methyl-butyl)chroman-4-one
IUPAC Name	(2~{R})-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-(3-hydroxy-3-methyl-butyl)chroman-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 49 51 0 0 0 0 0 0 0 0999 V2000 -6.5376 -0.2839 -1.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5983 0.2108 -0.0018 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9386 -0.3543 1.3412 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6338 1.6006 0.0833 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1498 -0.1659 -0.3176 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3122 0.3686 0.8069 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8881 0.0609 0.6034 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4355 -1.2288 0.8405 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3220 -2.2343 1.2697 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1018 -1.5116 0.6492 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7931 -0.5236 0.2229 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1358 -0.8176 0.0326 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0441 0.2921 0.1234 C 0 0 1 0 0 0 0 0 0 0 0 0 4.4327 -0.1416 -0.0468 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9015 -1.2544 0.6192 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2064 -1.6978 0.4837 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0971 -1.0351 -0.3321 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4113 -1.4207 -0.5143 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6440 0.0776 -1.0037 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5229 0.7710 -1.8383 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3236 0.5175 -0.8601 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5893 1.3420 -0.8629 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2328 1.7798 -0.4458 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8365 2.9711 -0.4494 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3025 0.7508 -0.0029 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0361 1.0538 0.1842 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4279 2.3600 -0.0691 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4593 -0.6288 -0.5656 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7513 0.5808 -1.7590 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0426 -1.1098 -1.6211 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6539 0.3712 2.1445 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4126 -1.3024 1.5240 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0306 -0.5305 1.4641 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2636 2.0164 -0.5485 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8488 0.2513 -1.2795 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0691 -1.2678 -0.3525 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6496 -0.0924 1.7739 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4456 1.4511 0.8640 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3314 -3.0609 0.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2786 -2.5190 0.8292 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8722 0.7603 1.1394 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1907 -1.7726 1.2621 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5251 -2.5657 1.0200 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1473 -1.2271 0.1544 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2425 1.6790 -2.1809 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0561 1.3959 -1.4240 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2986 2.1983 -0.8883 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4991 0.8577 -1.8569 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2435 3.0280 0.6911 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 2 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 1 0 19 21 2 0 13 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 26 7 1 0 25 11 1 0 21 14 1 0 1 28 1 0 1 29 1 0 1 30 1 0 3 31 1 0 3 32 1 0 3 33 1 0 4 34 1 0 5 35 1 0 5 36 1 0 6 37 1 0 6 38 1 0 9 39 1 0 10 40 1 0 13 41 1 1 15 42 1 0 16 43 1 0 18 44 1 0 20 45 1 0 21 46 1 0 22 47 1 0 22 48 1 0 27 49 1 0 M END

Standard InCHIKey	AUWAYTAMBAVTLA-MRXNPFEDSA-N
Standard InCHI	InChI=1S/C20H22O7/c1-20(2,26)6-5-11-13(22)8-17-18(19(11)25)15(24)9-16(27-17)10-3-4-12(21)14(23)7-10/h3-4,7-8,16,21-23,25-26H,5-6,9H2,1-2H3/t16-/m1/s1
SMILES	CC(C)(O)CCC1=C(O)C=C2O[C@@H](C3=CC=C(O)C(O)=C3)CC(=O)C2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.14	Volume:	371.883 ? Van der Waals volume.
Dense:	1.006	LogP:	1.891 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.245 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.393 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	18.0
TPSA:	127.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.521	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.363	Fsp³:	0.35
MCE-18:	69.259 ? 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:	0.583	Fluc inhibitor:	0.6 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.662 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.255 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.142	Promiscuous compounds:	0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.206	MDCK Permeability:	-4.83
Pgp-inhibitor:	0.044	Pgp-substrate:	0.003
PAMPA:	0.305 ? 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):	0.029
20% Bioavailability (F20%):	0.71	30% Bioavailability (F30%):	0.986
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.821
Plasma Protein Binding (PPB):	96.268%	Volume Distribution (VD):	-0.19
Fu:	3.699% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.689
BSEP inhibitor:	0.605

ADMET: Metabolism

CYP1A2-inhibitor:	0.876	CYP1A2-substrate:	0.86
CYP2C19-inhibitor:	0.008	CYP2C19-substrate:	0.078
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.979
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.909
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.98 ? 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):

12.204

Half-life (T1/2):

1.478

ADMET: Toxicity

hERG Blockers:	0.047	hERG Blockers (10um):	0.504
Human Hepatotoxicity (H-HT):	0.807	Drug-induced Liver Injury (DILI):	0.248
AMES Toxicity:	0.754	Rat Oral Acute Toxicity:	0.468
Maximum Recommended Daily Dose:	0.76	Skin Sensitization:	0.99
Carcinogencity:	0.377	Eye Corrosion:	0.006
Eye Irritation:	0.972	Respiratory Toxicity:	0.882
Drug-induced Neurotoxicity:	0.038	Ototoxicity:	0.798
Hematotoxicity:	0.103	Drug-induced Nephrotoxicity:	0.546
Genotoxicity:	0.97	RPMI-8226 Immunitoxicity:	0.091
A549 Cytotoxicity:	0.782	Hek293 Cytotoxicity:	0.326
BCF:	0.784 ? 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:	3.361 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.898 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.148 ? 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
NPO19912	Vellozia nanuzae	Species	Velloziaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19912	Vellozia nanuzae	Species	Velloziaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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

Molecular-level activity

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

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 NPC538289 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	18088
0.1-0.2	26578
0.2-0.3	4380
0.3-0.4	601
0.4-0.5	159
0.5-0.6	40
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
0.7273	Intermediate Similarity	NPC261063
0.6716	Remote Similarity	NPC213896
0.6667	Remote Similarity	NPC321779
0.6271	Remote Similarity	NPC321011
0.6271	Remote Similarity	NPC294852
0.6271	Remote Similarity	NPC188679
0.6232	Remote Similarity	NPC472629
0.6154	Remote Similarity	NPC125855
0.6143	Remote Similarity	NPC488556
0.5938	Remote Similarity	NPC1089
0.5833	Remote Similarity	NPC471209
0.5833	Remote Similarity	NPC472627
0.5811	Remote Similarity	NPC488557
0.5797	Remote Similarity	NPC35038
0.5733	Remote Similarity	NPC27337
0.5733	Remote Similarity	NPC472598
0.5658	Remote Similarity	NPC488555
0.5658	Remote Similarity	NPC484418
0.5634	Remote Similarity	NPC228504
0.5574	Remote Similarity	NPC324386
0.5522	Remote Similarity	NPC610133
0.5467	Remote Similarity	NPC472628
0.5441	Remote Similarity	NPC223500
0.5441	Remote Similarity	NPC480158
0.541	Remote Similarity	NPC1612
0.541	Remote Similarity	NPC183959
0.5405	Remote Similarity	NPC185276
0.5333	Remote Similarity	NPC278778
0.5333	Remote Similarity	NPC488558
0.5333	Remote Similarity	NPC298692
0.5323	Remote Similarity	NPC482119
0.5323	Remote Similarity	NPC482120
0.5303	Remote Similarity	NPC480991
0.5238	Remote Similarity	NPC192083
0.5217	Remote Similarity	NPC166689
0.5205	Remote Similarity	NPC290133
0.5195	Remote Similarity	NPC45849
0.5195	Remote Similarity	NPC195796
0.519	Remote Similarity	NPC474055
0.5161	Remote Similarity	NPC312391
0.5147	Remote Similarity	NPC21350
0.5135	Remote Similarity	NPC64915
0.5125	Remote Similarity	NPC472634
0.5067	Remote Similarity	NPC224851
0.5067	Remote Similarity	NPC164272
0.5067	Remote Similarity	NPC470327
0.5065	Remote Similarity	NPC488554
0.5065	Remote Similarity	NPC472630
0.5062	Remote Similarity	NPC321399

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC538289 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3573
0.1-0.2	5413
0.2-0.3	152
0.3-0.4	7
0.4-0.5	3
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
0.5238	Remote Similarity	NPD2393	Clinical (unspecified phase)

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