NPASS Compound

Natural Product: NPC307215

Natural Product ID	NPC307215
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GRBCXNICXUJJIW-KGLIPLIRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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 50 52 0 0 0 0 0 0 0 0999 V2000 0.5373 0.7629 0.3157 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0177 1.0133 -1.0515 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1820 0.0806 -1.3056 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2435 0.3010 -0.3118 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2423 1.2232 -0.5365 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2547 1.4298 0.4112 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2334 0.6925 1.5750 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2305 -0.2487 1.8244 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2580 -0.4168 0.8643 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2250 -0.9832 3.0028 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1832 -1.9233 3.1955 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2099 0.8807 2.5073 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2994 1.7410 2.4635 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0483 0.8655 -2.1031 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5007 1.1355 -3.4958 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6070 -0.4804 -2.0903 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0511 -1.3474 -2.8408 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7421 -0.8824 -1.2863 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0960 -2.2401 -1.2396 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1945 -2.6070 -0.5002 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9588 -1.6731 0.1978 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6211 -0.3414 0.1576 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5053 0.0244 -0.5948 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5301 0.3690 0.9260 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6209 -0.4810 1.1879 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0860 -1.7703 1.0006 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2714 0.9015 1.0905 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3298 1.5191 0.5398 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8729 -0.2715 0.4319 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3661 2.0625 -1.0861 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6020 0.2017 -2.3229 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8384 -0.9781 -1.2356 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2257 1.7816 -1.4598 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9977 2.1584 0.1771 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4844 -1.1663 1.0950 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3192 -2.4834 4.1450 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2339 -2.6241 2.3130 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2272 -1.3695 3.1453 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0926 2.7683 2.8290 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1898 1.3848 2.9916 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6078 1.8562 1.3864 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8133 1.6495 -1.9125 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0102 0.2735 -3.9207 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3798 1.3624 -4.1324 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1473 2.0309 -3.5098 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4901 -2.9424 -1.7878 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5005 -3.6632 -0.4408 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2900 1.0893 -0.6080 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0193 -0.3398 2.2185 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3985 -0.3260 0.4160 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 7 12 1 0 12 13 1 0 2 14 1 0 14 15 1 0 14 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 1 0 9 4 1 0 23 18 1 0 26 21 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 1 3 31 1 0 3 32 1 0 5 33 1 0 6 34 1 0 9 35 1 0 11 36 1 0 11 37 1 0 11 38 1 0 13 39 1 0 13 40 1 0 13 41 1 0 14 42 1 1 15 43 1 0 15 44 1 0 15 45 1 0 19 46 1 0 20 47 1 0 23 48 1 0 25 49 1 0 25 50 1 0 M END

Standard InCHIKey	GRBCXNICXUJJIW-KGLIPLIRSA-N
Standard InCHI	InChI=1S/C21H24O5/c1-13(9-15-5-7-17(23-3)19(10-15)24-4)14(2)21(22)16-6-8-18-20(11-16)26-12-25-18/h5-8,10-11,13-14H,9,12H2,1-4H3/t13-,14+/m1/s1
SMILES	C[C@H](Cc1ccc(c(c1)OC)OC)[C@H](C)C(=O)c1ccc2c(c1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	356.16	Volume:	371.599 ? Van der Waals volume.
Dense:	0.958	LogP:	3.365 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.303 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.169 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	17.0
TPSA:	53.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.698	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.936	Fsp³:	0.381
MCE-18:	55.241 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.133	Fluc inhibitor:	0.661 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.039 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.198 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.356	Promiscuous compounds:	0.13

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.851	MDCK Permeability:	-4.666
Pgp-inhibitor:	0.512	Pgp-substrate:	0.043
PAMPA:	0.034 ? 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%):	0.026	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.536

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.409	MRP1:	0.454
Plasma Protein Binding (PPB):	93.894%	Volume Distribution (VD):	0.196
Fu:	5.774% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.96
OATP1B3 inhibitor:	0.942	BCRP inhibitor:	0.077
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.394	CYP1A2-substrate:	0.997
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.988
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.217	CYP2C8-inhibitor:	1.0
HLM stability:	0.934 ? 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):

5.673

Half-life (T1/2):

0.639

ADMET: Toxicity

hERG Blockers:	0.326	hERG Blockers (10um):	0.539
Human Hepatotoxicity (H-HT):	0.677	Drug-induced Liver Injury (DILI):	0.934
AMES Toxicity:	0.671	Rat Oral Acute Toxicity:	0.293
Maximum Recommended Daily Dose:	0.393	Skin Sensitization:	0.774
Carcinogencity:	0.61	Eye Corrosion:	0.058
Eye Irritation:	0.903	Respiratory Toxicity:	0.679
Drug-induced Neurotoxicity:	0.903	Ototoxicity:	0.459
Hematotoxicity:	0.595	Drug-induced Nephrotoxicity:	0.741
Genotoxicity:	0.845	RPMI-8226 Immunitoxicity:	0.176
A549 Cytotoxicity:	0.264	Hek293 Cytotoxicity:	0.523
BCF:	2.088 ? 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:	4.308 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.802 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.242 ? 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
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5619	Chrysosplenium japonicum	Species	Saxifragaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5619	Chrysosplenium japonicum	Species	Saxifragaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5619	Chrysosplenium japonicum	Species	Saxifragaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5619	Chrysosplenium japonicum	Species	Saxifragaceae	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 NPC307215 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	23618
0.1-0.2	22949
0.2-0.3	2832
0.3-0.4	346
0.4-0.5	74
0.5-0.6	22
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.907	High Similarity	NPC485482
0.75	Intermediate Similarity	NPC344161
0.7358	Intermediate Similarity	NPC46880
0.7255	Intermediate Similarity	NPC28398
0.6591	Remote Similarity	NPC80241
0.6591	Remote Similarity	NPC301641
0.6591	Remote Similarity	NPC485483
0.6415	Remote Similarity	NPC474990
0.5926	Remote Similarity	NPC274356
0.5926	Remote Similarity	NPC101748
0.5909	Remote Similarity	NPC165106
0.5769	Remote Similarity	NPC249788
0.569	Remote Similarity	NPC100425
0.5556	Remote Similarity	NPC104077
0.5556	Remote Similarity	NPC219671
0.5556	Remote Similarity	NPC147616
0.5556	Remote Similarity	NPC485480
0.5417	Remote Similarity	NPC477886
0.541	Remote Similarity	NPC106739
0.5333	Remote Similarity	NPC474691
0.5333	Remote Similarity	NPC487677
0.5333	Remote Similarity	NPC487675
0.5306	Remote Similarity	NPC604144
0.52	Remote Similarity	NPC40352
0.52	Remote Similarity	NPC213711
0.5185	Remote Similarity	NPC196937
0.5172	Remote Similarity	NPC205915
0.5094	Remote Similarity	NPC476748
0.5088	Remote Similarity	NPC143895
0.5079	Remote Similarity	NPC471505

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC307215 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3669
0.1-0.2	5186
0.2-0.3	274
0.3-0.4	18
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
0.5909	Remote Similarity	NPD5283	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