NPASS Compound

Natural Product: NPC484150

Natural Product ID	NPC484150
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LXIQXFWXXPJPEE-KHPOWYRWSA-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:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0001789] Trichothecenes

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 74 79 0 0 0 0 0 0 0 0999 V2000 -5.5509 3.5591 0.2160 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8401 2.2608 0.0955 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5240 1.4916 1.1328 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8096 0.2197 0.8191 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5440 0.4745 -0.0255 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9336 1.3110 -1.1748 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4148 1.7103 -1.2152 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7116 1.2915 0.9251 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4261 1.4018 0.8959 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7380 1.8518 0.3855 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6645 2.6043 -0.5695 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0547 1.4965 0.8807 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2790 1.6643 0.7283 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2972 2.3659 -0.0699 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7085 1.8804 0.1200 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9847 0.5129 0.2871 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7077 -0.1266 0.3692 C 0 0 2 0 0 0 0 0 0 0 0 0 4.7277 -1.5780 0.8484 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5553 -2.1261 0.0718 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9563 -3.3955 0.2724 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6796 -3.5368 0.4932 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6456 -2.5562 0.5828 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8745 -1.3818 0.5038 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7089 -2.7033 0.7518 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5716 -1.6579 0.7987 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9192 -2.2463 1.2564 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9350 -1.9137 0.2283 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0589 -1.7181 -0.9974 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5324 -1.8523 -2.2504 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7271 -2.9370 -1.5888 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9542 -0.8715 -0.3991 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9630 -0.7950 -1.5243 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6343 -0.7502 0.3663 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2016 0.0343 -0.9713 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1779 0.3462 -1.7889 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0168 -0.0160 -1.7689 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1762 0.6613 1.5524 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4725 -0.0473 2.4529 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2185 4.0116 1.1786 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3374 4.1916 -0.6541 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6591 3.4092 0.3406 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7933 1.8127 2.1423 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3685 -0.0524 1.8431 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7527 0.9323 -2.1831 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4040 2.3130 -1.1490 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0450 0.8692 -1.5539 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4897 2.5043 -1.9868 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0402 1.0039 1.9912 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2207 2.3267 0.8602 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8607 0.7861 1.7949 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3870 3.4656 0.3399 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0388 2.5954 -1.1087 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2572 2.1689 -0.8270 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2730 2.4749 0.9040 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6550 -2.0299 0.4676 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5734 -1.6884 1.9202 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7951 -1.3638 0.2751 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9519 -2.1090 -0.9799 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5456 -4.3544 0.2532 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3065 -4.5393 0.6380 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3260 -0.9016 1.6067 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8858 -3.3811 1.2703 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1615 -2.0032 2.2974 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6436 -2.7480 0.0070 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6016 -2.2036 -2.4121 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0492 -1.7013 -3.2212 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5630 -1.7985 -1.7220 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5460 -0.6274 -2.4911 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2931 0.0465 -1.5213 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9868 0.9638 -2.3904 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0892 -0.7498 -2.6530 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0263 -0.0993 -1.4241 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8751 1.3056 2.0680 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6183 0.2412 3.3890 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 6 6 7 1 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 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 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 6 27 33 1 0 17 34 1 6 34 35 2 0 34 36 1 0 17 37 1 0 37 38 1 0 7 2 1 0 37 13 1 0 33 4 1 0 31 5 1 0 31 25 1 0 28 30 1 1 1 39 1 0 1 40 1 0 1 41 1 0 3 42 1 0 4 43 1 1 6 44 1 0 6 45 1 0 7 46 1 0 7 47 1 0 8 48 1 0 8 49 1 0 12 50 1 0 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 18 55 1 0 18 56 1 0 19 57 1 0 19 58 1 0 20 59 1 0 21 60 1 0 25 61 1 1 26 62 1 0 26 63 1 0 27 64 1 6 29 65 1 0 29 66 1 0 32 67 1 0 32 68 1 0 32 69 1 0 36 70 1 0 36 71 1 0 36 72 1 0 37 73 1 1 38 74 1 0 M END

Standard InCHIKey	LXIQXFWXXPJPEE-KHPOWYRWSA-N
Standard InCHI	InChI=1S/C29H36O9/c1-17-7-10-27-15-34-24(32)13-19-8-11-35-28(18(2)30,25(19)33)9-5-4-6-23(31)38-20-14-22(37-21(27)12-17)29(16-36-29)26(20,27)3/h4,6,12-13,20-22,25,33H,5,7-11,14-16H2,1-3H3/b6-4-,19-13+/t20-,21-,22-,25-,26-,27-,28-,29+/m1/s1
SMILES	CC1=C[C@@H]2[C@@]3(CC1)COC(=O)/C=C/1CCO[C@](CC/C=CC(=O)O[C@@H]4C[C@H]([C@@]5(CO5)[C@@]34C)O2)(C(=O)C)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	528.24	Volume:	522.095 ? Van der Waals volume.
Dense:	1.012	LogP:	1.372 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.812 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.593 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	38.0
TPSA:	120.89 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.311	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.655	Fsp³:	0.69
MCE-18:	144.061 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.649	Fluc inhibitor:	0.015 ? 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:	0.089 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.141	Promiscuous compounds:	0.794

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.102	MDCK Permeability:	-4.815
Pgp-inhibitor:	0.05	Pgp-substrate:	0.423
PAMPA:	0.464 ? 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%):	0.949	30% Bioavailability (F30%):	0.368
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.034	MRP1:	0.915
Plasma Protein Binding (PPB):	89.276%	Volume Distribution (VD):	0.15
Fu:	8.376% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.056
OATP1B3 inhibitor:	0.0	BCRP inhibitor:	0.001
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.025
HLM stability:	0.139 ? 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):

4.865

Half-life (T1/2):

2.643

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.097
Human Hepatotoxicity (H-HT):	0.972	Drug-induced Liver Injury (DILI):	0.883
AMES Toxicity:	0.974	Rat Oral Acute Toxicity:	0.616
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	1.0
Carcinogencity:	0.337	Eye Corrosion:	0.0
Eye Irritation:	0.396	Respiratory Toxicity:	0.606
Drug-induced Neurotoxicity:	0.185	Ototoxicity:	0.771
Hematotoxicity:	0.42	Drug-induced Nephrotoxicity:	0.977
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.875
A549 Cytotoxicity:	0.607	Hek293 Cytotoxicity:	0.748
BCF:	0.683 ? 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:	3.453 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.319 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.631 ? 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
NPO6563	Paramyrothecium roridum	Species	Stachybotryaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31117520]
NPO6563	Paramyrothecium roridum	Species	Stachybotryaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6563	Paramyrothecium roridum	Species	Stachybotryaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6563	Paramyrothecium roridum	Species	Stachybotryaceae	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	2

Activity Type	# Activity
Cell line	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
NPT111	Cell line	K562	Homo sapiens	IC50	=	1.3	nM	PMID[31117520]
NPT2482	Cell line	SW 1116	Homo sapiens	IC50	=	1.5	nM	PMID[31117520]

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 NPC484150 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	19099
0.1-0.2	29517
0.2-0.3	1177
0.3-0.4	18
0.4-0.5	16
0.5-0.6	12
0.6-0.7	10
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC474286
0.9091	High Similarity	NPC475130
0.9091	High Similarity	NPC484151
0.9079	High Similarity	NPC484144
0.8462	Intermediate Similarity	NPC484155
0.7317	Intermediate Similarity	NPC484923
0.7317	Intermediate Similarity	NPC484922
0.7093	Intermediate Similarity	NPC484145
0.6854	Remote Similarity	NPC484154
0.6456	Remote Similarity	NPC98813
0.6456	Remote Similarity	NPC600365
0.6353	Remote Similarity	NPC29389
0.6353	Remote Similarity	NPC112316
0.631	Remote Similarity	NPC469959
0.631	Remote Similarity	NPC469957
0.6092	Remote Similarity	NPC472263
0.6067	Remote Similarity	NPC484149
0.6024	Remote Similarity	NPC484152
0.593	Remote Similarity	NPC98038
0.593	Remote Similarity	NPC313921
0.5914	Remote Similarity	NPC484153
0.5914	Remote Similarity	NPC484925
0.5862	Remote Similarity	NPC13743
0.573	Remote Similarity	NPC108682
0.5579	Remote Similarity	NPC484142
0.5579	Remote Similarity	NPC484146
0.5543	Remote Similarity	NPC101965
0.5543	Remote Similarity	NPC101400
0.5333	Remote Similarity	NPC9579
0.51	Remote Similarity	NPC484147

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC484150 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7147
0.1-0.2	1993
0.2-0.3	10
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