NPASS Compound

Natural Product: NPC36021

Natural Product ID	NPC36021
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HJXBCJUBOCBSHO-HUDRDOLLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	56640968
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0002051] Agarofurans

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 71 75 0 0 0 0 0 0 0 0999 V2000 -2.7258 -2.9791 0.3960 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7007 -1.9239 0.7936 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4581 -0.7344 1.3090 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5552 0.4747 1.3046 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1301 0.8541 -0.0909 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8004 -0.3210 -0.9585 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7932 -0.3931 -2.1391 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5437 -0.1267 -1.6346 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9626 -1.3332 -2.4227 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5757 -2.6472 -1.8614 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8493 -2.7139 -1.3404 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6958 -1.6413 -0.2515 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6161 -1.7894 0.2116 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2513 -2.7727 -0.4816 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9204 -4.1464 0.1019 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7136 -2.7015 -0.6053 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4568 0.2593 -0.6609 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1491 1.4294 -0.5866 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9804 2.2783 -1.4673 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0714 1.6252 0.5493 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2199 0.6460 1.5054 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0779 0.8197 2.5675 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8091 1.9827 2.6962 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6564 2.9551 1.7396 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8016 2.7915 0.6742 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0565 1.6921 -0.7394 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8628 2.9699 -1.1295 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7848 3.5240 -0.9268 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9232 3.7118 -1.7947 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1966 3.2056 -2.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8775 4.2220 -2.7105 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0808 5.2370 -2.7798 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9149 4.9889 -2.2539 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4575 0.1447 2.1411 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1903 0.7855 3.3428 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9807 1.7052 3.6841 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9338 0.4699 4.2307 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6035 -2.8492 1.0814 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0517 -2.8867 -0.6386 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3135 -3.9784 0.6439 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1404 -2.3267 1.6913 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7476 -0.9333 2.3583 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3724 -0.6124 0.7303 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0827 1.2992 1.8236 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2117 1.4575 0.0185 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3123 -0.7976 -3.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9462 0.7020 -2.3938 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7402 -0.8474 -1.8583 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4316 0.7082 -2.3552 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6153 -1.2641 -3.4729 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0809 -1.3145 -2.4943 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8375 -3.4539 -2.5283 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6254 -2.5293 -2.0523 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9929 -3.7182 -0.9008 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7716 -4.8880 -0.7255 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0746 -4.1521 0.7799 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8000 -4.5502 0.6816 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9876 -2.9417 -1.6751 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2388 -3.5211 -0.0291 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2300 -1.7900 -0.3425 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6559 -0.2813 1.4301 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1978 0.0471 3.3257 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4904 2.1309 3.5318 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2345 3.8857 1.8328 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6818 3.5516 -0.0742 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5749 2.2117 -1.8695 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8900 4.1820 -3.0748 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0921 5.6754 -2.1946 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6457 -0.2230 3.7800 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4496 1.4386 4.4987 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5680 0.0200 5.1997 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 1 0 5 6 1 0 6 7 1 6 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 13 14 1 0 14 15 1 0 14 16 1 0 8 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 5 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 1 0 4 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 12 2 1 0 25 20 1 0 33 29 2 0 12 6 1 0 14 10 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 1 3 42 1 0 3 43 1 0 4 44 1 1 5 45 1 1 7 46 1 0 7 47 1 0 7 48 1 0 8 49 1 6 9 50 1 0 9 51 1 0 10 52 1 6 11 53 1 0 11 54 1 0 15 55 1 0 15 56 1 0 15 57 1 0 16 58 1 0 16 59 1 0 16 60 1 0 21 61 1 0 22 62 1 0 23 63 1 0 24 64 1 0 25 65 1 0 30 66 1 0 31 67 1 0 33 68 1 0 37 69 1 0 37 70 1 0 37 71 1 0 M END

Standard InCHIKey	HJXBCJUBOCBSHO-HUDRDOLLSA-N
Standard InCHI	InChI=1S/C29H34O8/c1-17-13-22(34-18(2)30)24(36-26(32)20-11-12-33-16-20)28(5)23(35-25(31)19-9-7-6-8-10-19)14-21-15-29(17,28)37-27(21,3)4/h6-12,16-17,21-24H,13-15H2,1-5H3/t17-,21-,22-,23+,24+,28-,29+/m1/s1
SMILES	C[C@@H]1C[C@H]([C@@H]([C@@]2(C)[C@H](C[C@@H]3C[C@]12OC3(C)C)OC(=O)c1ccccc1)OC(=O)c1ccoc1)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	510.23	Volume:	516.588 ? Van der Waals volume.
Dense:	0.988	LogP:	3.611 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.542 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.86 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	28.0
TPSA:	101.27 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.411	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.712	Fsp³:	0.552
MCE-18:	152.622 ? 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:	0.564	Fluc inhibitor:	0.158 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.021 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.226	Promiscuous compounds:	0.105

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.177	MDCK Permeability:	-4.744
Pgp-inhibitor:	0.988	Pgp-substrate:	0.596
PAMPA:	0.206 ? 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%):	0.275	30% Bioavailability (F30%):	0.316
50% Bioavailability (F50%):	0.97

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.793	MRP1:	0.999
Plasma Protein Binding (PPB):	93.639%	Volume Distribution (VD):	-0.031
Fu:	5.374% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.423	BCRP inhibitor:	0.504
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.782
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.032
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.007
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.01
CYP3A4-inhibitor:	0.927	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.984 ? 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):

6.319

Half-life (T1/2):

0.549

ADMET: Toxicity

hERG Blockers:	0.159	hERG Blockers (10um):	0.71
Human Hepatotoxicity (H-HT):	0.081	Drug-induced Liver Injury (DILI):	0.96
AMES Toxicity:	0.31	Rat Oral Acute Toxicity:	0.403
Maximum Recommended Daily Dose:	0.781	Skin Sensitization:	0.873
Carcinogencity:	0.815	Eye Corrosion:	0.001
Eye Irritation:	0.598	Respiratory Toxicity:	0.36
Drug-induced Neurotoxicity:	0.509	Ototoxicity:	0.184
Hematotoxicity:	0.03	Drug-induced Nephrotoxicity:	0.394
Genotoxicity:	0.535	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.231	Hek293 Cytotoxicity:	0.299
BCF:	0.989 ? 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:	4.057 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.421 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.065 ? 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
NPO26437	Maytenus jelskii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20146433]
NPO26437	Maytenus jelskii	Species	Celastraceae	Eukaryota	fruits	n.a.	n.a.	PMID[21856049]
NPO26437	Maytenus jelskii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27541714]
NPO40471	Celastrus subspicata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28548851]
NPO26437	Maytenus jelskii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26437	Maytenus jelskii	Species	Celastraceae	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
Others	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
NPT2	Others	Unspecified	n.a.	IC50	=	34500.0	nM	PMID[28548851]

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 NPC36021 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	17992
0.1-0.2	29742
0.2-0.3	1688
0.3-0.4	298
0.4-0.5	98
0.5-0.6	24
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.875	High Similarity	NPC481070
0.8125	Intermediate Similarity	NPC481066
0.7703	Intermediate Similarity	NPC276735
0.7639	Intermediate Similarity	NPC481071
0.7465	Intermediate Similarity	NPC66985
0.7432	Intermediate Similarity	NPC481068
0.7143	Intermediate Similarity	NPC481069
0.6338	Remote Similarity	NPC156077
0.6081	Remote Similarity	NPC243165
0.6	Remote Similarity	NPC483879
0.5972	Remote Similarity	NPC147561
0.5775	Remote Similarity	NPC481065
0.5765	Remote Similarity	NPC56953
0.5682	Remote Similarity	NPC86800
0.5679	Remote Similarity	NPC214550
0.5647	Remote Similarity	NPC483872
0.5625	Remote Similarity	NPC481061
0.5584	Remote Similarity	NPC481067
0.5581	Remote Similarity	NPC473089
0.5581	Remote Similarity	NPC483874
0.5412	Remote Similarity	NPC608007
0.5294	Remote Similarity	NPC483887
0.5294	Remote Similarity	NPC158020
0.5275	Remote Similarity	NPC294512
0.5275	Remote Similarity	NPC479045
0.5195	Remote Similarity	NPC195647
0.5195	Remote Similarity	NPC200592
0.5195	Remote Similarity	NPC610542
0.519	Remote Similarity	NPC37641
0.519	Remote Similarity	NPC473860
0.5125	Remote Similarity	NPC472577
0.5109	Remote Similarity	NPC176413
0.5057	Remote Similarity	NPC14499
0.5053	Remote Similarity	NPC483891

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC36021 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3212
0.1-0.2	5815
0.2-0.3	123
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