NPASS Compound

Natural Product: NPC161056

Natural Product ID	NPC161056
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OJKXLUIFUZRGOO-SFTDATJTSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44474259
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

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 63 65 0 0 0 0 0 0 0 0999 V2000 0.6875 0.1329 4.3950 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1014 0.1650 3.1358 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7855 1.1631 2.8812 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0745 -0.8876 2.2715 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7688 -0.9908 1.0468 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3233 0.0941 0.1329 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0088 0.0678 -1.2105 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4695 0.2111 -1.1040 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0843 1.4348 -1.1378 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4420 1.5378 -1.0332 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2706 0.3989 -0.8863 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6216 -0.8528 -0.8535 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2797 -0.8937 -0.9612 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4388 -1.9787 -0.7090 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8183 -3.2510 -0.6741 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5610 0.4812 -0.7851 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8122 0.7912 -0.7025 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1552 0.0642 -0.0163 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6802 -1.2299 -0.5907 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1578 -1.2179 -0.7205 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8201 -0.7760 -1.8660 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1993 -0.7778 -1.9503 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9701 -1.2183 -0.9005 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3489 -1.6584 0.2377 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9889 -1.6514 0.3076 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2969 -2.0561 1.1707 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5233 -2.1844 0.4633 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3402 -1.3457 -0.6682 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7293 1.2854 -0.7000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3695 2.3990 0.1020 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7562 3.6786 -0.2666 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4278 3.7866 -1.3298 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4011 4.8820 0.5491 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4574 0.9536 4.4005 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0042 0.3643 5.2570 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1416 -0.8646 4.5737 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8488 -0.9381 1.3069 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5051 -1.9918 0.6180 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5844 1.0813 0.5892 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5873 0.8998 -1.8090 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8157 -0.8641 -1.7684 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5151 2.3725 -1.2488 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9536 2.5073 -1.0591 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7901 -1.8768 -0.9322 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3689 -3.3880 0.3127 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0629 -3.3693 -1.4897 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5700 -4.0709 -0.8176 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4372 0.0260 -0.1168 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3965 0.9253 -1.6760 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0744 1.7785 -0.1769 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5804 0.1037 1.0318 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2447 -1.4656 -1.5928 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4364 -2.0907 0.0604 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2557 -0.4270 -2.7014 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7273 -0.4400 -2.8265 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4969 -2.0017 1.2118 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3068 -1.7845 1.1413 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6546 -3.2358 0.2102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3648 1.4609 -1.7088 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8456 1.1451 -0.7036 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7060 4.5989 1.3475 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3089 5.2988 1.0275 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9868 5.6898 -0.0885 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 12 14 1 0 14 15 1 0 11 16 1 0 16 17 1 0 6 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 27 28 1 0 18 29 1 0 29 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 13 8 1 0 25 20 1 0 28 23 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 0 5 38 1 0 6 39 1 1 7 40 1 0 7 41 1 0 9 42 1 0 10 43 1 0 13 44 1 0 15 45 1 0 15 46 1 0 15 47 1 0 17 48 1 0 17 49 1 0 17 50 1 0 18 51 1 1 19 52 1 0 19 53 1 0 21 54 1 0 22 55 1 0 25 56 1 0 27 57 1 0 27 58 1 0 29 59 1 0 29 60 1 0 33 61 1 0 33 62 1 0 33 63 1 0 M END

Standard InCHIKey	OJKXLUIFUZRGOO-SFTDATJTSA-N
Standard InCHI	InChI=1S/C25H30O8/c1-16(26)30-13-20(9-18-5-7-22(28-3)24(11-18)29-4)21(14-31-17(2)27)10-19-6-8-23-25(12-19)33-15-32-23/h5-8,11-12,20-21H,9-10,13-15H2,1-4H3/t20-,21-/m0/s1
SMILES	CC(=O)OC[C@H](Cc1ccc(c(c1)OC)OC)[C@@H](Cc1ccc2c(c1)OCO2)COC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	458.19	Volume:	464.517 ? Van der Waals volume.
Dense:	0.986	LogP:	2.623 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.826 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.687 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	18.0
TPSA:	89.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.472	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.265	Fsp³:	0.44
MCE-18:	58.056 ? 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:	0.334	Fluc inhibitor:	0.036 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.335 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.329	Promiscuous compounds:	0.136

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.764	MDCK Permeability:	-4.63
Pgp-inhibitor:	0.978	Pgp-substrate:	0.088
PAMPA:	0.025 ? 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):	0.0
20% Bioavailability (F20%):	0.042	30% Bioavailability (F30%):	0.031
50% Bioavailability (F50%):	0.675

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012	MRP1:	0.863
Plasma Protein Binding (PPB):	95.51%	Volume Distribution (VD):	-0.221
Fu:	5.613% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.238
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.108	CYP1A2-substrate:	0.796
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.407
CYP2C9-inhibitor:	0.044	CYP2C9-substrate:	0.991
CYP2D6-inhibitor:	0.082	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.994	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.364	CYP2C8-inhibitor:	0.56
HLM stability:	0.853 ? 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):

2.834

Half-life (T1/2):

0.93

ADMET: Toxicity

hERG Blockers:	0.164	hERG Blockers (10um):	0.337
Human Hepatotoxicity (H-HT):	0.727	Drug-induced Liver Injury (DILI):	0.754
AMES Toxicity:	0.915	Rat Oral Acute Toxicity:	0.093
Maximum Recommended Daily Dose:	0.115	Skin Sensitization:	0.943
Carcinogencity:	0.675	Eye Corrosion:	0.002
Eye Irritation:	0.611	Respiratory Toxicity:	0.019
Drug-induced Neurotoxicity:	0.608	Ototoxicity:	0.622
Hematotoxicity:	0.437	Drug-induced Nephrotoxicity:	0.755
Genotoxicity:	0.93	RPMI-8226 Immunitoxicity:	0.06
A549 Cytotoxicity:	0.036	Hek293 Cytotoxicity:	0.134
BCF:	0.88 ? 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:	3.903 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.472 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.981 ? 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
NPO12785	Bursera fagaroides	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12785	Bursera fagaroides	Species	Burseraceae	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 NPC161056 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	18447
0.1-0.2	27967
0.2-0.3	2728
0.3-0.4	497
0.4-0.5	150
0.5-0.6	38
0.6-0.7	17
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9024	High Similarity	NPC476748
0.8667	High Similarity	NPC143895
0.7917	Intermediate Similarity	NPC205915
0.7391	Intermediate Similarity	NPC11453
0.7273	Intermediate Similarity	NPC600801
0.7083	Intermediate Similarity	NPC192255
0.7083	Intermediate Similarity	NPC110958
0.7083	Intermediate Similarity	NPC19890
0.7045	Intermediate Similarity	NPC344161
0.6923	Remote Similarity	NPC176586
0.6923	Remote Similarity	NPC210354
0.6792	Remote Similarity	NPC191158
0.6792	Remote Similarity	NPC177644
0.6786	Remote Similarity	NPC487679
0.6786	Remote Similarity	NPC487678
0.6744	Remote Similarity	NPC81067
0.6744	Remote Similarity	NPC602945
0.6471	Remote Similarity	NPC158737
0.6458	Remote Similarity	NPC223807
0.6316	Remote Similarity	NPC145569
0.6207	Remote Similarity	NPC56184
0.6136	Remote Similarity	NPC80241
0.6136	Remote Similarity	NPC301641
0.6136	Remote Similarity	NPC485483
0.6102	Remote Similarity	NPC282291
0.6102	Remote Similarity	NPC166137
0.5962	Remote Similarity	NPC171550
0.5962	Remote Similarity	NPC211386
0.5962	Remote Similarity	NPC134764
0.5893	Remote Similarity	NPC185908
0.5893	Remote Similarity	NPC482891
0.5769	Remote Similarity	NPC474288
0.5714	Remote Similarity	NPC18576
0.566	Remote Similarity	NPC92693
0.5614	Remote Similarity	NPC47181
0.5614	Remote Similarity	NPC230968
0.5614	Remote Similarity	NPC102260
0.5577	Remote Similarity	NPC482890
0.5556	Remote Similarity	NPC40237
0.5532	Remote Similarity	NPC604144
0.5517	Remote Similarity	NPC3982
0.5455	Remote Similarity	NPC165128
0.5455	Remote Similarity	NPC165106
0.5417	Remote Similarity	NPC40352
0.5417	Remote Similarity	NPC213711
0.5385	Remote Similarity	NPC196937
0.5385	Remote Similarity	NPC227160
0.5385	Remote Similarity	NPC82111
0.5323	Remote Similarity	NPC169973
0.5294	Remote Similarity	NPC57119
0.5294	Remote Similarity	NPC158471
0.5294	Remote Similarity	NPC226862
0.5273	Remote Similarity	NPC274356
0.5273	Remote Similarity	NPC101748
0.5254	Remote Similarity	NPC5310
0.5254	Remote Similarity	NPC300776
0.5254	Remote Similarity	NPC176814
0.5254	Remote Similarity	NPC4982
0.5254	Remote Similarity	NPC606629
0.5246	Remote Similarity	NPC40094
0.5094	Remote Similarity	NPC249788
0.5094	Remote Similarity	NPC485482
0.5094	Remote Similarity	NPC483654
0.5088	Remote Similarity	NPC206882

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC161056 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3695
0.1-0.2	5083
0.2-0.3	337
0.3-0.4	31
0.4-0.5	2
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
0.5455	Remote Similarity	NPD5283	Phase 2
0.5075	Remote Similarity	NPD5563	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