NPASS Compound

Natural Product: NPC581378

Natural Product ID	NPC581378
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-[2,6-dihydroxy-4-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]-3-phenyl-propane-1,3-dione
IUPAC Name	1-[2,6-dihydroxy-4-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]-3-phenyl-propane-1,3-dione
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 53 55 0 0 0 0 0 0 0 0999 V2000 -5.5304 -1.6656 -2.3385 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1591 -0.6745 -1.6653 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7535 -0.3145 -1.6058 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0124 -0.9731 -0.5103 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6133 -1.7553 0.2532 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5988 -0.7234 -0.3104 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6443 -1.4999 -0.9288 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0872 -2.5356 -1.7550 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7285 -1.2854 -0.7568 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1985 -0.2760 0.0485 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5364 -0.0070 0.2640 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5676 -0.7228 -0.3060 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3131 -1.2775 0.7470 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5335 -0.3387 1.7628 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7685 -0.8331 2.5265 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5404 -2.0984 3.0647 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8753 1.0165 1.2114 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7877 1.6135 2.0771 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4759 0.9009 -0.1861 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7109 2.2051 -0.6502 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4767 0.2427 -1.0851 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1006 -0.4866 -2.0997 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2186 0.5109 0.6752 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1203 0.2883 0.4967 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0964 1.0781 1.1257 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1733 0.0897 -0.9566 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7709 1.1665 -0.1990 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7001 1.9194 0.4847 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0320 1.5733 0.3943 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4372 0.4824 -0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5245 -0.2719 -1.0561 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5458 0.7700 -1.5518 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2042 -0.6333 -2.5542 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6048 -3.3055 -1.3228 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4244 -1.9332 -1.2729 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3192 -1.5537 -0.9681 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7083 -0.2809 2.4744 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0252 -0.1646 3.3579 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6127 -0.9534 1.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8708 -2.5719 2.5111 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0116 1.6927 1.1378 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7809 2.5981 2.0134 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4096 0.2936 -0.1819 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5961 2.2196 -1.1174 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8098 1.0071 -1.5626 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6994 -1.3801 -2.2111 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5542 1.3074 1.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8828 2.0084 1.4220 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7159 1.4682 -0.1026 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3552 2.7729 1.0819 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7746 2.1639 0.9324 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5040 0.2409 -0.4188 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8136 -1.1141 -1.6519 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 14 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 10 23 1 0 23 24 2 0 24 25 1 0 2 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 24 6 1 0 31 26 1 0 21 12 1 0 3 32 1 0 3 33 1 0 8 34 1 0 9 35 1 0 12 36 1 6 14 37 1 1 15 38 1 0 15 39 1 0 16 40 1 0 17 41 1 6 18 42 1 0 19 43 1 1 20 44 1 0 21 45 1 6 22 46 1 0 23 47 1 0 25 48 1 0 27 49 1 0 28 50 1 0 29 51 1 0 30 52 1 0 31 53 1 0 M END

Standard InCHIKey	HAVNCBAQNUDYRJ-JOZSIVFUSA-N
Standard InCHI	InChI=1S/C21H22O10/c22-9-16-18(27)19(28)20(29)21(31-16)30-11-6-13(24)17(14(25)7-11)15(26)8-12(23)10-4-2-1-3-5-10/h1-7,16,18-22,24-25,27-29H,8-9H2/t16-,18+,19-,20+,21+/m0/s1
SMILES	O=C(CC(=O)C1=C(O)C=C(O[C@@H]2O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C1O)C1=CC=CC=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.12	Volume:	412.913 ? Van der Waals volume.
Dense:	1.051	LogP:	1.322 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.698 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.661 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	20.0
TPSA:	173.98 ? 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:	0.251	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.757	Fsp³:	0.333
MCE-18:	70.5 ? 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:	0.552	Fluc inhibitor:	0.643 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.175 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.682 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.151	Promiscuous compounds:	0.328

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.175	MDCK Permeability:	-5.133
Pgp-inhibitor:	0.001	Pgp-substrate:	0.02
PAMPA:	0.996 ? 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):	0.015
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.513
50% Bioavailability (F50%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.294
Plasma Protein Binding (PPB):	86.833%	Volume Distribution (VD):	-0.527
Fu:	10.368% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.026
BSEP inhibitor:	0.036

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.388
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.794
HLM stability:	0.01 ? 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):

2.954

Half-life (T1/2):

2.621

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.275
Human Hepatotoxicity (H-HT):	0.152	Drug-induced Liver Injury (DILI):	0.122
AMES Toxicity:	0.561	Rat Oral Acute Toxicity:	0.057
Maximum Recommended Daily Dose:	0.014	Skin Sensitization:	0.942
Carcinogencity:	0.023	Eye Corrosion:	0.0
Eye Irritation:	0.579	Respiratory Toxicity:	0.671
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.593
Hematotoxicity:	0.144	Drug-induced Nephrotoxicity:	0.175
Genotoxicity:	0.215	RPMI-8226 Immunitoxicity:	0.033
A549 Cytotoxicity:	0.195	Hek293 Cytotoxicity:	0.298
BCF:	0.452 ? 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:	3.177 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.652 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.884 ? 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
NPO46193	Malus sp.	Species	Rosaceae	Eukaryota	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

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 NPC581378 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	14465
0.1-0.2	30177
0.2-0.3	4213
0.3-0.4	728
0.4-0.5	226
0.5-0.6	39
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
0.7377	Intermediate Similarity	NPC479374
0.6552	Remote Similarity	NPC214454
0.6462	Remote Similarity	NPC121001
0.6	Remote Similarity	NPC97052
0.5938	Remote Similarity	NPC222455
0.5714	Remote Similarity	NPC23084
0.569	Remote Similarity	NPC294470
0.5522	Remote Similarity	NPC199335
0.5507	Remote Similarity	NPC600107
0.5441	Remote Similarity	NPC190217
0.541	Remote Similarity	NPC226712
0.541	Remote Similarity	NPC608788
0.5405	Remote Similarity	NPC106625
0.5373	Remote Similarity	NPC218003
0.5352	Remote Similarity	NPC99233
0.5345	Remote Similarity	NPC212729
0.5345	Remote Similarity	NPC142319
0.5345	Remote Similarity	NPC604498
0.5333	Remote Similarity	NPC9248
0.5294	Remote Similarity	NPC477240
0.527	Remote Similarity	NPC219163
0.527	Remote Similarity	NPC39351
0.527	Remote Similarity	NPC26195
0.5263	Remote Similarity	NPC300537
0.5254	Remote Similarity	NPC269242
0.5231	Remote Similarity	NPC205054
0.5224	Remote Similarity	NPC106025
0.5217	Remote Similarity	NPC134260
0.5211	Remote Similarity	NPC302989
0.5205	Remote Similarity	NPC169248
0.5205	Remote Similarity	NPC72649
0.5179	Remote Similarity	NPC228907
0.5161	Remote Similarity	NPC12308
0.5143	Remote Similarity	NPC8497
0.5143	Remote Similarity	NPC610808
0.5139	Remote Similarity	NPC57587
0.5135	Remote Similarity	NPC259182
0.5132	Remote Similarity	NPC29830
0.5082	Remote Similarity	NPC152722
0.5077	Remote Similarity	NPC218685
0.507	Remote Similarity	NPC604892
0.5068	Remote Similarity	NPC148273
0.5068	Remote Similarity	NPC606353

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC581378 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2822
0.1-0.2	6042
0.2-0.3	272
0.3-0.4	11
0.4-0.5	2
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
0.541	Remote Similarity	NPD1091	Pre-clinical

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