NPASS Compound

Natural Product: NPC85624

Natural Product ID	NPC85624
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Sid85149094
IUPAC Name	6-[(2R)-2,3-dihydroxy-3-methylbutyl]-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1159420
PubChem CID	44144279
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives [CHEMONTID:0001743] Coumarin glycosides

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 56 58 0 0 0 0 0 0 0 0999 V2000 -4.5005 -1.9486 -1.2429 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0331 -1.8405 -0.9014 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2503 -1.9526 -2.1895 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8108 -0.4222 -0.3551 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3454 -0.2060 -0.0548 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0723 1.1476 0.4850 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1652 1.9534 0.7334 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9802 3.2203 1.2444 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0931 4.0156 1.4878 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8604 5.2740 1.9982 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5714 5.6692 2.2353 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3718 6.8389 2.7084 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5597 4.8891 1.9916 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6977 3.6833 1.5076 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3732 2.8588 1.2503 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2213 1.5557 0.7272 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3108 0.8645 0.5238 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8519 -0.2966 0.0912 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8868 -0.0631 -1.0414 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2393 -1.4499 -1.5259 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7806 -2.2773 -0.3988 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1108 -2.0623 0.9105 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1070 -2.3643 2.0115 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1214 -1.4034 1.9033 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6487 -0.7903 1.1396 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5854 -3.6304 -0.7635 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2627 -1.3348 -2.4907 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3785 0.7312 -2.0397 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2180 0.4188 -1.3869 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6811 -2.7968 0.0208 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6939 -1.7291 -2.3164 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1282 -1.2681 -0.6333 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8964 -2.9664 -1.0519 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1127 -0.9625 -2.6619 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2451 -2.3370 -1.9180 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7755 -2.5964 -2.9215 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4857 -0.3303 0.4850 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9349 -0.9938 0.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8166 -0.2455 -1.0387 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2032 1.6364 0.5469 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0722 3.6400 1.2778 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7030 5.9407 2.2077 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3681 3.2432 1.4647 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2061 -1.0875 -0.3123 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8275 0.3527 -0.5744 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3765 -1.9206 -2.0502 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8798 -2.1347 -0.3584 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2595 -2.7779 1.0415 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6595 -2.2318 3.0234 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5902 -3.3520 1.8726 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8322 -0.6266 1.3697 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9436 -3.8075 -1.6748 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0812 -0.9291 -2.0991 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8647 1.5996 -2.0650 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1739 0.3725 -1.5572 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3150 -2.7694 0.7790 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 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 21 26 1 0 20 27 1 0 19 28 1 0 4 29 1 0 2 30 1 0 16 6 1 0 25 18 1 0 14 8 2 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 3 35 1 0 3 36 1 0 4 37 1 1 5 38 1 0 5 39 1 0 7 40 1 0 9 41 1 0 10 42 1 0 15 43 1 0 18 44 1 6 19 45 1 1 20 46 1 6 21 47 1 1 22 48 1 1 23 49 1 0 23 50 1 0 24 51 1 0 26 52 1 0 27 53 1 0 28 54 1 0 29 55 1 0 30 56 1 0 M END

Standard InCHIKey	DMCVVAVPFHUPNH-UPPPXSOGSA-N
Standard InCHI	InChI=1S/C20H26O10/c1-20(2,27)14(22)6-10-5-9-3-4-15(23)28-11(9)7-12(10)29-19-18(26)17(25)16(24)13(8-21)30-19/h3-5,7,13-14,16-19,21-22,24-27H,6,8H2,1-2H3/t13-,14-,16-,17+,18-,19-/m1/s1
SMILES	CC(C)([C@@H](Cc1cc2ccc(=O)oc2cc1O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	426.15	Volume:	403.527 ? Van der Waals volume.
Dense:	1.056	LogP:	-0.597 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.659 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.988 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	18.0
TPSA:	170.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.303	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.136	Fsp³:	0.55
MCE-18:	76.419 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.691	Fluc inhibitor:	0.164 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.972 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.063 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.121	Promiscuous compounds:	0.177

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.182	MDCK Permeability:	-5.074
Pgp-inhibitor:	0.0	Pgp-substrate:	0.002
PAMPA:	0.987 ? 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):	0.003
20% Bioavailability (F20%):	0.343	30% Bioavailability (F30%):	0.897
50% Bioavailability (F50%):	0.898

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.899
Plasma Protein Binding (PPB):	62.446%	Volume Distribution (VD):	-0.434
Fu:	39.998% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.384
HLM stability:	0.042 ? 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):

2.612

Half-life (T1/2):

3.159

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.072
Human Hepatotoxicity (H-HT):	0.665	Drug-induced Liver Injury (DILI):	0.712
AMES Toxicity:	0.883	Rat Oral Acute Toxicity:	0.05
Maximum Recommended Daily Dose:	0.183	Skin Sensitization:	0.971
Carcinogencity:	0.334	Eye Corrosion:	0.0
Eye Irritation:	0.034	Respiratory Toxicity:	0.035
Drug-induced Neurotoxicity:	0.019	Ototoxicity:	0.932
Hematotoxicity:	0.199	Drug-induced Nephrotoxicity:	0.597
Genotoxicity:	0.912	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.172	Hek293 Cytotoxicity:	0.243
BCF:	0.157 ? 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:	2.545 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.256 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.193 ? 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
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	roots	Miyazaki prefecture, Japan	n.a.	PMID[9873511]
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3509	Angelica furcijuga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3509	Angelica furcijuga	Species	Apiaceae	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

Activity Type	# Activity
Potency	2
IC50	2
Inhibition	2

Activity Type	# Activity
Individual protein	2
Organism	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	5.8	nM	PMID[20000782]
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	7079.5	nM	PMID[23823011]

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
NPT32	Organism	Mus musculus	Mus musculus	IC50	>	100000.0	nM	PMID[18178092]
NPT32	Organism	Mus musculus	Mus musculus	Inhibition	=	49.0	%	PMID[18178092]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	IC50	>	100000.0	nM	PMID[18178092]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Inhibition	=	5.8	%	PMID[18178092]

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 NPC85624 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	17866
0.1-0.2	28513
0.2-0.3	2610
0.3-0.4	758
0.4-0.5	92
0.5-0.6	15
0.6-0.7	3
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
0.6377	Remote Similarity	NPC103409
0.6197	Remote Similarity	NPC96294
0.6154	Remote Similarity	NPC296377
0.5667	Remote Similarity	NPC609477
0.5652	Remote Similarity	NPC78746
0.56	Remote Similarity	NPC212670
0.56	Remote Similarity	NPC206264
0.5455	Remote Similarity	NPC485744
0.5405	Remote Similarity	NPC52740
0.5385	Remote Similarity	NPC469699
0.5286	Remote Similarity	NPC253574
0.5286	Remote Similarity	NPC98179
0.5263	Remote Similarity	NPC41844
0.5161	Remote Similarity	NPC485746
0.5122	Remote Similarity	NPC470264
0.5063	Remote Similarity	NPC213197
0.5057	Remote Similarity	NPC284810
0.5055	Remote Similarity	NPC485745

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC85624 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4249
0.1-0.2	4787
0.2-0.3	103
0.3-0.4	9
0.4-0.5	1
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
0.56	Remote Similarity	NPD1653	Approved

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