NPASS Compound

Natural Product: NPC601984

Natural Product ID	NPC601984
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KTIHIXHZDCHISY-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL4536141
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 67 72 0 0 0 0 0 0 0 0999 V2000 -6.0735 4.9473 0.3963 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7095 4.5413 0.2843 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4545 3.1748 0.1382 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4720 2.2465 0.1058 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2108 0.8801 -0.0400 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9233 0.4191 -0.1566 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5673 -0.9964 -0.3100 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5055 -2.0164 -0.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1583 -3.3480 -0.5001 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0196 -4.2658 -0.5409 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8203 -3.6453 -0.5984 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3670 -4.9397 -0.7429 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3082 -5.9577 -0.7870 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0117 -5.1806 -0.8365 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0952 -4.1491 -0.7887 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2370 -4.3195 -0.8806 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0038 -5.4802 -1.0182 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5586 -2.8221 -0.6394 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4008 -1.7363 -0.5553 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9224 -1.0419 -1.6014 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4856 -1.3633 -2.8760 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0255 -0.6485 -3.9698 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8598 -0.0509 -1.3535 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2927 0.2672 -0.0842 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1709 1.1901 0.1612 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6047 1.5146 1.3758 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6093 2.5836 1.5155 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0965 3.0115 2.7157 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0562 4.0313 2.7918 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5458 4.6413 1.6584 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4808 5.6367 1.7180 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0485 4.2024 0.4496 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0973 3.1933 0.3580 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1058 0.8435 2.4641 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1669 -0.1536 2.2820 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6728 -0.8064 3.2546 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7658 -0.4343 0.9954 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8385 -1.4107 0.7170 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3203 -2.1050 1.8166 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8916 -2.5912 -0.5479 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3144 -1.3649 -0.4102 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9095 1.3430 -0.1244 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1679 2.6882 0.0193 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1900 6.0382 0.4381 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5885 4.4957 -0.4952 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5501 4.5329 1.3056 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5088 2.5954 0.1998 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0280 0.1799 -0.0592 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5421 -1.7599 -0.2798 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8644 -6.0389 -1.6347 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6843 -6.1969 -0.9498 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5010 -6.1834 -1.7225 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2943 -5.9601 -0.0785 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9441 -5.1830 -1.5334 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5158 -0.9848 -4.9046 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0437 0.4333 -3.8340 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0933 -0.9629 -4.0970 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2786 0.5067 -2.1862 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7383 2.5586 3.6293 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4194 4.3461 3.7646 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1264 5.8314 2.4558 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4381 4.6870 -0.4543 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7259 2.8671 -0.6017 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4327 1.0798 3.4861 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6112 -1.8308 2.1335 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8791 0.9843 -0.2140 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3738 3.4364 0.0465 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 15 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 20 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 30 32 1 0 32 33 2 0 26 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 2 0 38 39 1 0 18 40 2 0 40 41 1 0 6 42 1 0 42 43 2 0 43 3 1 0 41 7 1 0 40 11 1 0 38 19 1 0 37 24 1 0 33 27 1 0 1 44 1 0 1 45 1 0 1 46 1 0 4 47 1 0 5 48 1 0 8 49 1 0 13 50 1 0 14 51 1 0 17 52 1 0 17 53 1 0 17 54 1 0 22 55 1 0 22 56 1 0 22 57 1 0 23 58 1 0 28 59 1 0 29 60 1 0 31 61 1 0 32 62 1 0 33 63 1 0 34 64 1 0 39 65 1 0 42 66 1 0 43 67 1 0 M END

Standard InCHIKey	KTIHIXHZDCHISY-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C33H24O10/c1-39-19-10-6-17(7-11-19)24-12-20(35)28-21(36)14-25(40-2)31(33(28)43-24)30-26(41-3)15-27-29(32(30)38)22(37)13-23(42-27)16-4-8-18(34)9-5-16/h4-15,34,36,38H,1-3H3
SMILES	COc1ccc(-c2cc(=O)c3c(O)cc(OC)c(-c4c(OC)cc5oc(-c6ccc(O)cc6)cc(=O)c5c4O)c3o2)cc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	580.14	Volume:	573.704 ? Van der Waals volume.
Dense:	1.011	LogP:	4.159 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.884 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.716 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	36.0
TPSA:	148.8 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.213	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.968	Fsp³:	0.091
MCE-18:	36.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.989	Fluc inhibitor:	0.284 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.874 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.998 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.307	Promiscuous compounds:	0.835

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.036	MDCK Permeability:	-4.768
Pgp-inhibitor:	0.438	Pgp-substrate:	0.177
PAMPA:	0.072 ? 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):	0.006
20% Bioavailability (F20%):	0.247	30% Bioavailability (F30%):	0.6
50% Bioavailability (F50%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.896
Plasma Protein Binding (PPB):	97.969%	Volume Distribution (VD):	-0.135
Fu:	1.44% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.949
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	0.351
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.013
CYP2C9-inhibitor:	0.991	CYP2C9-substrate:	0.946
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.304
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.343 ? 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):

2.837

Half-life (T1/2):

1.506

ADMET: Toxicity

hERG Blockers:	0.134	hERG Blockers (10um):	0.472
Human Hepatotoxicity (H-HT):	0.486	Drug-induced Liver Injury (DILI):	0.995
AMES Toxicity:	0.703	Rat Oral Acute Toxicity:	0.576
Maximum Recommended Daily Dose:	0.963	Skin Sensitization:	0.304
Carcinogencity:	0.9	Eye Corrosion:	0.001
Eye Irritation:	0.948	Respiratory Toxicity:	0.865
Drug-induced Neurotoxicity:	0.032	Ototoxicity:	0.074
Hematotoxicity:	0.133	Drug-induced Nephrotoxicity:	0.044
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.128
A549 Cytotoxicity:	0.488	Hek293 Cytotoxicity:	0.934
BCF:	1.356 ? 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:	4.576 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.44 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.044 ? 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
NPO47795	Araucaria excelsa	Species	Araucariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO64012	Wollemia nobilis	Species	Araucariaceae	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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Single protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT30107	Single protein	Amyloid-beta A4 protein	Homo sapiens	IC50	>	50000.0	nM	PMID[31138471]

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 NPC601984 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	29803
0.1-0.2	17033
0.2-0.3	2228
0.3-0.4	579
0.4-0.5	167
0.5-0.6	34
0.6-0.7	10
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
0.7903	Intermediate Similarity	NPC610914
0.7097	Intermediate Similarity	NPC52611
0.6986	Remote Similarity	NPC159707
0.6849	Remote Similarity	NPC158027
0.6712	Remote Similarity	NPC603508
0.6575	Remote Similarity	NPC248739
0.6462	Remote Similarity	NPC234133
0.6364	Remote Similarity	NPC601565
0.6308	Remote Similarity	NPC29353
0.6234	Remote Similarity	NPC215203
0.6154	Remote Similarity	NPC205026
0.6104	Remote Similarity	NPC186227
0.5974	Remote Similarity	NPC290830
0.5875	Remote Similarity	NPC265624
0.5844	Remote Similarity	NPC600972
0.5823	Remote Similarity	NPC121649
0.5732	Remote Similarity	NPC55443
0.5696	Remote Similarity	NPC194593
0.557	Remote Similarity	NPC600396
0.5507	Remote Similarity	NPC231772
0.5507	Remote Similarity	NPC198826
0.5507	Remote Similarity	NPC57030
0.5507	Remote Similarity	NPC145379
0.5507	Remote Similarity	NPC120163
0.55	Remote Similarity	NPC14606
0.5429	Remote Similarity	NPC108406
0.5429	Remote Similarity	NPC78913
0.5375	Remote Similarity	NPC72425
0.5375	Remote Similarity	NPC303485
0.5366	Remote Similarity	NPC18699
0.5362	Remote Similarity	NPC127447
0.5342	Remote Similarity	NPC67322
0.5286	Remote Similarity	NPC184136
0.5286	Remote Similarity	NPC250266
0.5278	Remote Similarity	NPC195202
0.5278	Remote Similarity	NPC223579
0.5211	Remote Similarity	NPC603662
0.5205	Remote Similarity	NPC137062
0.5185	Remote Similarity	NPC71061
0.5143	Remote Similarity	NPC241498
0.5143	Remote Similarity	NPC156222
0.5143	Remote Similarity	NPC47815
0.507	Remote Similarity	NPC266597
0.507	Remote Similarity	NPC604085
0.5068	Remote Similarity	NPC124784
0.5062	Remote Similarity	NPC150908

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC601984 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5734
0.1-0.2	3350
0.2-0.3	59
0.3-0.4	6
0.4-0.5	1
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