NPASS Compound

Natural Product: NPC606146

Natural Product ID	NPC606146
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KABPASQHFAUTDF-XZUXRINTSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL4850577
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 58 61 0 0 0 0 0 0 0 0999 V2000 4.9885 -3.2735 1.4067 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5606 -2.0644 0.9908 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8474 -1.0300 0.4005 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4840 -1.0951 0.1631 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7986 -0.0547 -0.4244 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3673 -0.0936 -0.6864 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9104 -1.2767 -1.2449 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4676 -1.0601 -1.2783 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8387 -0.3634 -0.0006 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5380 -0.0701 0.6040 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4496 1.3291 1.0962 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8547 1.7276 0.8860 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3303 1.0445 -0.2281 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7874 1.1496 -0.2992 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4231 2.3521 -0.0936 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7936 2.4961 -0.1512 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5713 1.3880 -0.4273 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9738 1.4901 -0.4955 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6837 1.2869 0.6923 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1818 1.3758 0.7162 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0691 1.0300 1.7402 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9625 0.1675 -0.6383 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7700 -0.9400 -0.9161 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1367 -2.1852 -1.1306 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 0.0480 -0.5742 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5187 1.0678 -0.7737 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8848 1.1700 -0.5519 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5419 0.1081 0.0394 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9197 0.2103 0.2635 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8333 -0.2025 -0.6881 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3158 -0.0966 -0.4562 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4021 -0.6756 -1.7684 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3256 -3.6427 0.5955 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4298 -3.0988 2.3400 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8389 -3.9952 1.5506 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9464 -1.9767 0.4429 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0426 0.7549 -1.2943 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6437 -0.3814 -2.1633 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9950 -2.0264 -1.4140 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4666 -0.9454 0.6725 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8533 -0.8164 1.3215 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0954 2.0208 0.4797 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7505 1.4839 2.1375 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8872 1.4224 -1.1717 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8263 3.2178 0.1214 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3044 3.4380 0.0090 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4034 2.4703 0.8362 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6312 0.9979 -0.2105 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5462 0.8606 1.6235 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4933 -2.3901 -0.2267 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8867 -2.9994 -1.1524 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5394 -2.1897 -2.0555 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1485 -0.9445 -0.7505 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0282 1.8964 -1.2308 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4636 2.0435 -0.8201 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5361 -0.3378 0.5988 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6482 0.9510 -0.6951 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8663 -0.7732 -1.1178 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 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 18 19 1 0 19 20 1 0 19 21 2 0 17 22 1 0 22 23 1 0 23 24 1 0 22 25 2 0 5 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 1 0 30 31 1 0 30 32 2 0 28 3 1 0 10 6 1 0 25 14 1 0 13 9 1 0 1 33 1 0 1 34 1 0 1 35 1 0 4 36 1 0 6 37 1 6 8 38 1 0 8 39 1 0 9 40 1 1 10 41 1 1 11 42 1 0 11 43 1 0 13 44 1 6 15 45 1 0 16 46 1 0 20 47 1 0 20 48 1 0 20 49 1 0 24 50 1 0 24 51 1 0 24 52 1 0 25 53 1 0 26 54 1 0 27 55 1 0 31 56 1 0 31 57 1 0 31 58 1 0 M END

Standard InCHIKey	KABPASQHFAUTDF-XZUXRINTSA-N
Standard InCHI	InChI=1S/C24H26O8/c1-13(25)31-19-7-5-15(9-21(19)27-3)23-17-11-30-24(18(17)12-29-23)16-6-8-20(32-14(2)26)22(10-16)28-4/h5-10,17-18,23-24H,11-12H2,1-4H3/t17-,18-,23+,24+/m0/s1
SMILES	COc1cc([C@H]2OC[C@H]3[C@@H]2CO[C@@H]3c2ccc(OC(C)=O)c(OC)c2)ccc1OC(C)=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.16	Volume:	438.664 ? Van der Waals volume.
Dense:	1.008	LogP:	1.595 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.929 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.866 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	23.0
TPSA:	89.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.495	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.721	Fsp³:	0.417
MCE-18:	80.471 ? 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:	0.36	Fluc inhibitor:	0.303 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.029 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.367 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.255	Promiscuous compounds:	0.477

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.811	MDCK Permeability:	-4.725
Pgp-inhibitor:	0.302	Pgp-substrate:	0.502
PAMPA:	0.005 ? 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%):	0.029	30% Bioavailability (F30%):	0.165
50% Bioavailability (F50%):	0.659

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.66	MRP1:	0.953
Plasma Protein Binding (PPB):	63.295%	Volume Distribution (VD):	0.234
Fu:	35.426% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.991
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.097
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.767	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.994	CYP2C19-substrate:	0.918
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.71
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.994
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.938
HLM stability:	0.954 ? 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):

5.698

Half-life (T1/2):

0.604

ADMET: Toxicity

hERG Blockers:	0.02	hERG Blockers (10um):	0.169
Human Hepatotoxicity (H-HT):	0.715	Drug-induced Liver Injury (DILI):	0.982
AMES Toxicity:	0.802	Rat Oral Acute Toxicity:	0.417
Maximum Recommended Daily Dose:	0.183	Skin Sensitization:	0.966
Carcinogencity:	0.352	Eye Corrosion:	0.112
Eye Irritation:	0.938	Respiratory Toxicity:	0.207
Drug-induced Neurotoxicity:	0.399	Ototoxicity:	0.147
Hematotoxicity:	0.581	Drug-induced Nephrotoxicity:	0.199
Genotoxicity:	0.905	RPMI-8226 Immunitoxicity:	0.065
A549 Cytotoxicity:	0.559	Hek293 Cytotoxicity:	0.172
BCF:	0.866 ? 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:	3.799 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.123 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.703 ? 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
NPO21741	Araucaria angustifolia	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21741	Araucaria angustifolia	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21741	Araucaria angustifolia	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21741	Araucaria angustifolia	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21741	Araucaria angustifolia	Species	Araucariaceae	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
IC50	1

Activity Type	# Activity
Unchecked	1

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
NPT28438	Unchecked	Unchecked	n.a.	IC50	n.a.	n.a.	n.a.	PMID[33158578]

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 NPC606146 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	20146
0.1-0.2	27129
0.2-0.3	2232
0.3-0.4	214
0.4-0.5	75
0.5-0.6	38
0.6-0.7	15
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8158	Intermediate Similarity	NPC121783
0.8158	Intermediate Similarity	NPC34902
0.8158	Intermediate Similarity	NPC18449
0.7381	Intermediate Similarity	NPC222127
0.7381	Intermediate Similarity	NPC82862
0.6889	Remote Similarity	NPC227160
0.6889	Remote Similarity	NPC82111
0.6383	Remote Similarity	NPC488505
0.6364	Remote Similarity	NPC171928
0.6364	Remote Similarity	NPC158526
0.6364	Remote Similarity	NPC129687
0.6364	Remote Similarity	NPC33611
0.6364	Remote Similarity	NPC16830
0.6364	Remote Similarity	NPC100223
0.6327	Remote Similarity	NPC27843
0.6327	Remote Similarity	NPC7171
0.625	Remote Similarity	NPC189474
0.6098	Remote Similarity	NPC281864
0.6098	Remote Similarity	NPC328682
0.6098	Remote Similarity	NPC54321
0.5849	Remote Similarity	NPC474139
0.566	Remote Similarity	NPC298317
0.566	Remote Similarity	NPC255566
0.5652	Remote Similarity	NPC267064
0.5581	Remote Similarity	NPC216929
0.5581	Remote Similarity	NPC312713
0.5581	Remote Similarity	NPC126935
0.5581	Remote Similarity	NPC65933
0.5581	Remote Similarity	NPC57268
0.5581	Remote Similarity	NPC172676
0.5556	Remote Similarity	NPC483653
0.5455	Remote Similarity	NPC88640
0.5455	Remote Similarity	NPC101153
0.5455	Remote Similarity	NPC193666
0.5455	Remote Similarity	NPC123526
0.5455	Remote Similarity	NPC608725
0.5435	Remote Similarity	NPC473092
0.5435	Remote Similarity	NPC473093
0.5435	Remote Similarity	NPC8050
0.5345	Remote Similarity	NPC40094
0.5254	Remote Similarity	NPC276753
0.5254	Remote Similarity	NPC205796
0.5208	Remote Similarity	NPC148893
0.5208	Remote Similarity	NPC115207
0.5208	Remote Similarity	NPC158079
0.5208	Remote Similarity	NPC228346
0.5208	Remote Similarity	NPC40432
0.5208	Remote Similarity	NPC25333
0.5208	Remote Similarity	NPC161557
0.5208	Remote Similarity	NPC49235
0.5167	Remote Similarity	NPC246947
0.5106	Remote Similarity	NPC50683
0.5106	Remote Similarity	NPC112571
0.5106	Remote Similarity	NPC285725
0.5102	Remote Similarity	NPC165155
0.5102	Remote Similarity	NPC24490
0.5094	Remote Similarity	NPC14022
0.5094	Remote Similarity	NPC601703

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC606146 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3769
0.1-0.2	5070
0.2-0.3	308
0.3-0.4	3
0.4-0.5	0
0.5-0.6	0
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
		NPD

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