NPASS Compound

Natural Product: NPC479938

Natural Product ID	NPC479938
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JKCXNRZEWVHSJN-IKTUVGAPSA-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]

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 75 77 0 0 0 0 0 0 0 0999 V2000 3.9245 4.0910 0.3915 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7919 3.1409 0.2434 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6851 1.9724 -0.6092 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7538 1.1573 -0.5677 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6161 1.6127 -1.4913 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2717 1.2229 -1.0919 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0107 0.0297 -0.2571 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6026 -1.2176 -0.9828 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6443 0.0949 1.0643 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4356 1.3118 1.8911 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2440 -1.0816 1.9740 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7695 -1.1848 2.0403 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1525 -1.1231 3.0939 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1267 -1.3680 0.7168 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3185 -1.4891 0.9715 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1065 -0.4630 1.0022 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5397 0.8654 0.7786 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3817 0.9037 -0.1997 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5066 -0.2773 -0.2187 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6018 1.7031 0.3228 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0405 2.8005 1.0314 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4252 3.0148 2.1307 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1192 3.6809 0.6040 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7634 3.4759 -0.5237 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3915 2.3346 -1.3763 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4701 4.8381 1.5044 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5407 -2.9773 1.1900 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2192 -3.5444 0.1038 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4556 -4.1318 0.2934 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9307 -4.1331 1.4583 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2134 -4.7478 -0.8352 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2543 -3.4680 1.3391 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3863 -2.7686 0.2647 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3614 -3.1874 -0.8488 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1616 -4.0305 -1.8060 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3396 -4.4665 -1.7261 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6531 -4.4576 -2.9745 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1156 4.9117 1.0573 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0002 4.0741 -0.1544 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7197 3.2366 0.8384 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7230 0.2744 -1.1841 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6240 1.3508 0.0479 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0272 0.9476 -2.3293 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4440 2.5652 -2.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7595 2.1550 -0.7102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7285 1.0828 -2.0854 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8523 -1.7508 -1.5609 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2325 -1.8126 -0.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3329 -0.8687 -1.7550 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7332 -0.0589 0.9779 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0461 2.1719 1.3062 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8338 1.1389 2.8110 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4163 1.6507 2.2858 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6136 -0.8639 2.9881 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6933 -2.0272 1.6448 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1740 -0.6091 1.1936 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1591 1.2596 1.7710 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0820 1.8862 0.0303 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9076 1.0817 -1.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3154 -0.7480 -1.2451 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5600 4.1654 -0.7924 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0648 2.3514 -2.2693 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3393 2.4044 -1.7690 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5603 1.3512 -0.8817 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6421 5.5521 1.5323 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7073 4.4555 2.5195 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3703 5.3299 1.1197 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1324 -3.0840 2.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6306 -3.9863 -1.5147 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9763 -5.4532 -0.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4772 -5.3440 -1.4226 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4086 -3.1339 0.3096 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0035 -4.8008 -3.7954 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3543 -3.6652 -3.3087 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2862 -5.3237 -2.6243 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 17 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 23 26 1 0 15 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 27 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 19 7 1 0 19 14 1 0 33 14 1 0 1 38 1 0 1 39 1 0 2 40 1 0 4 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 6 45 1 0 6 46 1 0 8 47 1 0 8 48 1 0 8 49 1 0 9 50 1 0 10 51 1 0 10 52 1 0 10 53 1 0 11 54 1 0 11 55 1 0 16 56 1 0 17 57 1 1 18 58 1 0 18 59 1 0 19 60 1 0 24 61 1 0 25 62 1 0 25 63 1 0 25 64 1 0 26 65 1 0 26 66 1 0 26 67 1 0 27 68 1 1 31 69 1 0 31 70 1 0 31 71 1 0 33 72 1 6 37 73 1 0 37 74 1 0 37 75 1 0 M END

Standard InCHIKey	JKCXNRZEWVHSJN-IKTUVGAPSA-N
Standard InCHI	InChI=1S/C29H38O8/c1-9-16(3)11-12-28(8)18(5)13-24(32)29-22(26(34-19(6)30)37-27(29)35-20(7)31)14-21(15-23(28)29)36-25(33)17(4)10-2/h9-10,14,18,21,23,26-27H,1,3,11-13,15H2,2,4-8H3/b17-10-/t18?,21-,23?,26-,27+,28?,29?/m0/s1
SMILES	C=CC(=C)CCC1(C)C(C)CC(=O)C23C(=C[C@@H](CC12)OC(=O)/C(=CC)/C)[C@@H](OC(=O)C)O[C@H]3OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	514.26	Volume:	533.701 ? Van der Waals volume.
Dense:	0.964	LogP:	3.442 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.32 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.958 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	22.0
TPSA:	105.2 ? 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:	0.15	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.832	Fsp³:	0.586
MCE-18:	91.565 ? 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:	0.641	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.359 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.341	Promiscuous compounds:	0.394

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.905	MDCK Permeability:	-4.712
Pgp-inhibitor:	0.991	Pgp-substrate:	0.037
PAMPA:	0.067 ? 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):	0.011
20% Bioavailability (F20%):	0.924	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012	MRP1:	0.992
Plasma Protein Binding (PPB):	93.554%	Volume Distribution (VD):	0.142
Fu:	7.395% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.767
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.631
CYP2C19-inhibitor:	0.143	CYP2C19-substrate:	0.145
CYP2C9-inhibitor:	0.236	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.032
CYP3A4-inhibitor:	0.042	CYP3A4-substrate:	0.207
CYP2B6-substrate:	0.006	CYP2C8-inhibitor:	0.997
HLM stability:	0.998 ? 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):

6.891

Half-life (T1/2):

0.835

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.226
Human Hepatotoxicity (H-HT):	0.441	Drug-induced Liver Injury (DILI):	0.696
AMES Toxicity:	0.924	Rat Oral Acute Toxicity:	0.807
Maximum Recommended Daily Dose:	0.965	Skin Sensitization:	0.978
Carcinogencity:	0.461	Eye Corrosion:	0.001
Eye Irritation:	0.037	Respiratory Toxicity:	0.231
Drug-induced Neurotoxicity:	0.726	Ototoxicity:	0.422
Hematotoxicity:	0.287	Drug-induced Nephrotoxicity:	0.562
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.174
A549 Cytotoxicity:	0.62	Hek293 Cytotoxicity:	0.477
BCF:	1.027 ? 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:	3.969 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.892 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.349 ? 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
NPO40015	Anacolosa clarkii	Species	Aptandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30830773]

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
TGI	4

Activity Type	# Activity
Cell line	2
Others	2

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
NPT2276	Cell line	A673	Homo sapiens	TGI	=	3100.0	nM	PMID[30830773]
NPT15166	Cell line	Hep293TT	Homo sapiens	TGI	=	1800.0	nM	PMID[30830773]
NPT2	Others	Unspecified	n.a.	TGI	=	1900.0	nM	PMID[30830773]
NPT2	Others	Unspecified	n.a.	TGI	=	2000.0	nM	PMID[30830773]

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 NPC479938 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	23879
0.1-0.2	23427
0.2-0.3	2407
0.3-0.4	63
0.4-0.5	43
0.5-0.6	31
0.6-0.7	1
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8475	Intermediate Similarity	NPC479934
0.8333	Intermediate Similarity	NPC479935
0.8333	Intermediate Similarity	NPC479936
0.8333	Intermediate Similarity	NPC479939
0.8197	Intermediate Similarity	NPC479937
0.6667	Remote Similarity	NPC479941
0.5882	Remote Similarity	NPC171598
0.5714	Remote Similarity	NPC318917
0.5714	Remote Similarity	NPC481019
0.5634	Remote Similarity	NPC488236
0.5634	Remote Similarity	NPC479943
0.5556	Remote Similarity	NPC471366
0.5556	Remote Similarity	NPC476800
0.5556	Remote Similarity	NPC488237
0.5507	Remote Similarity	NPC472189
0.5479	Remote Similarity	NPC479940
0.5479	Remote Similarity	NPC7644
0.5429	Remote Similarity	NPC481018
0.5417	Remote Similarity	NPC472186
0.5405	Remote Similarity	NPC473545
0.5405	Remote Similarity	NPC475889
0.5405	Remote Similarity	NPC7613
0.5405	Remote Similarity	NPC479942
0.5352	Remote Similarity	NPC481020
0.5342	Remote Similarity	NPC488649
0.5278	Remote Similarity	NPC471362
0.5278	Remote Similarity	NPC471372
0.527	Remote Similarity	NPC481017
0.5205	Remote Similarity	NPC472188
0.52	Remote Similarity	NPC217921
0.52	Remote Similarity	NPC88013
0.52	Remote Similarity	NPC135015
0.5139	Remote Similarity	NPC132395
0.5139	Remote Similarity	NPC471364
0.5132	Remote Similarity	NPC48548
0.5067	Remote Similarity	NPC128795
0.5065	Remote Similarity	NPC472187

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479938 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7688
0.1-0.2	1439
0.2-0.3	23
0.3-0.4	0
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