NPASS Compound

Natural Product: NPC601097

Natural Product ID	NPC601097
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PXZNXGGXUQRNRY-KBJUPQRZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1952040
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 76 80 0 0 0 0 0 0 0 0999 V2000 10.7445 -2.3612 1.0188 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1094 -2.1652 -0.2527 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0193 -1.2842 -0.3393 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8511 -1.7103 0.0563 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7097 -3.5148 0.7278 Br 0 0 0 0 0 0 0 0 0 0 0 0 6.6562 -0.8862 0.0158 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6361 -1.5953 -0.6771 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8285 0.4705 -0.5105 C 0 0 1 0 0 0 0 0 0 0 0 0 8.1597 0.8526 -0.9233 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2008 0.0652 -0.8588 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9255 0.6586 -1.4321 Br 0 0 0 0 0 0 0 0 0 0 0 0 5.8319 0.6899 -1.6916 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5853 0.9615 -0.9375 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2450 0.7703 -1.4680 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0779 0.3453 -2.6215 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0755 1.0598 -0.6955 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7457 0.8676 -1.2313 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4468 -0.5394 -1.6285 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5399 -1.5182 -0.4765 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4160 -1.1398 0.5444 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6931 -1.5352 0.6626 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1992 -0.9330 1.7530 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.2570 -0.1649 2.3207 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3722 0.6789 3.5350 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8222 2.0460 3.0620 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0959 1.9416 2.3876 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.2740 1.4557 3.0177 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1952 1.1029 4.2206 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5402 1.3735 2.2720 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6697 0.9570 2.7255 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.6317 1.0255 1.7306 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9217 0.8850 0.4718 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.3909 -0.4690 0.3368 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5468 -1.1682 -0.7657 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8115 -2.9457 -0.8551 Br 0 0 0 0 0 0 0 0 0 0 0 0 -7.2737 -0.6203 -1.9042 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4379 -1.3348 -3.0468 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4845 -2.2198 -3.3322 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7766 0.5966 -1.8070 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7358 1.3024 -3.3313 Br 0 0 0 0 0 0 0 0 0 0 0 0 -7.6848 1.4699 -0.6372 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.0560 2.6501 -1.0622 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7014 1.7659 0.8493 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1211 -0.2928 1.5563 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9042 1.3908 0.2389 N 0 0 0 0 0 0 0 0 0 0 0 0 6.2566 1.4475 0.3855 O 0 0 0 0 0 0 0 0 0 0 0 0 11.5843 -3.0650 0.8994 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0971 -1.3925 1.3897 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9991 -2.7426 1.7655 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2448 -0.7987 1.0725 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7904 -2.5586 -0.4281 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3487 1.8828 -1.3293 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1664 1.5762 -2.2766 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7915 -0.1987 -2.3206 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2451 1.4161 0.2698 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5635 1.5129 -2.1181 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0095 1.1714 -0.4656 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6168 -0.5613 -1.9623 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0359 -0.8926 -2.4975 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5528 -1.5620 -0.0290 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2812 -2.5259 -0.9119 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2156 -2.2101 0.0080 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3721 0.7514 4.0097 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0491 0.1963 4.2370 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0757 2.4627 2.3896 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8789 2.7203 3.9664 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1742 2.2345 1.3799 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8354 -0.9628 1.1574 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4103 -2.7004 -4.3077 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6052 -2.9042 -2.4868 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4264 -1.5956 -3.3639 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7154 1.7127 -0.2543 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7853 2.6034 -1.9942 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9730 2.8302 0.7930 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8307 1.4813 0.2339 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8132 0.2156 1.7713 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 4 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 8 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 32 31 1 1 32 33 1 0 33 34 2 0 34 35 1 0 34 36 1 0 36 37 1 0 37 38 1 0 36 39 2 0 39 40 1 0 39 41 1 0 41 42 1 0 32 43 1 0 23 44 2 0 13 45 2 0 45 46 1 0 10 3 1 0 44 20 1 0 8 46 1 1 43 29 1 0 41 32 1 0 1 47 1 0 1 48 1 0 1 49 1 0 6 50 1 1 7 51 1 0 9 52 1 0 12 53 1 0 12 54 1 0 16 55 1 0 17 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 19 60 1 0 19 61 1 0 21 62 1 0 24 63 1 0 24 64 1 0 25 65 1 0 25 66 1 0 26 67 1 0 33 68 1 0 38 69 1 0 38 70 1 0 38 71 1 0 41 72 1 1 42 73 1 0 43 74 1 0 43 75 1 0 44 76 1 0 M END

Standard InCHIKey	PXZNXGGXUQRNRY-KBJUPQRZSA-N
Standard InCHI	InChI=1S/C28H30Br4N6O8/c1-43-21-15(29)8-27(23(39)19(21)31)10-17(36-45-27)25(41)33-5-3-7-38-12-14(35-13-38)4-6-34-26(42)18-11-28(46-37-18)9-16(30)22(44-2)20(32)24(28)40/h8-9,12-13,23-24,39-40H,3-7,10-11H2,1-2H3,(H,33,41)(H,34,42)/t23-,24-,27+,28+/m0/s1
SMILES	COC1=C(Br)[C@H](O)[C@@]2(C=C1Br)CC(C(=O)NCCCn1cnc(CCNC(=O)C3=NO[C@]4(C=C(Br)C(OC)=C(Br)[C@@H]4O)C3)c1)=NO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	893.89	Volume:	637.134 ? Van der Waals volume.
Dense:	1.403	LogP:	2.022 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.135 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.24 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	29.0
TPSA:	178.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.244	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.866	Fsp³:	0.464
MCE-18:	150.244 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.596	Fluc inhibitor:	0.021 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.103 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.454 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.236	Promiscuous compounds:	0.019

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.98	MDCK Permeability:	-4.761
Pgp-inhibitor:	0.148	Pgp-substrate:	0.391
PAMPA:	0.109 ? 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):	0.002
20% Bioavailability (F20%):	0.415	30% Bioavailability (F30%):	0.914
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.208	MRP1:	1.0
Plasma Protein Binding (PPB):	96.72%	Volume Distribution (VD):	-0.197
Fu:	1.885% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.98	BCRP inhibitor:	0.869
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.053
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.989
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.997
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.895
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.805
HLM stability:	0.794 ? 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):

0.822

Half-life (T1/2):

3.886

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.219
Human Hepatotoxicity (H-HT):	0.693	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	1.0	Rat Oral Acute Toxicity:	0.986
Maximum Recommended Daily Dose:	0.998	Skin Sensitization:	1.0
Carcinogencity:	0.999	Eye Corrosion:	0.0
Eye Irritation:	0.066	Respiratory Toxicity:	0.977
Drug-induced Neurotoxicity:	0.977	Ototoxicity:	0.768
Hematotoxicity:	0.055	Drug-induced Nephrotoxicity:	0.925
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.213
A549 Cytotoxicity:	0.541	Hek293 Cytotoxicity:	0.986
BCF:	0.936 ? 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:	3.857 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.48 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.962 ? 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
NPO56431	Pseudoceratina sp.	Genus	Pseudoceratinidae	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
Inhibition	1

Activity Type	# Activity
Organism	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
NPT471	Organism	Trypanosoma brucei brucei	Trypanosoma brucei brucei	Inhibition	=	80.0	%	PMID[22204643]

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 NPC601097 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	25688
0.1-0.2	24082
0.2-0.3	33
0.3-0.4	5
0.4-0.5	26
0.5-0.6	21
0.6-0.7	3
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
0.6235	Remote Similarity	NPC600759
0.6184	Remote Similarity	NPC1702
0.6026	Remote Similarity	NPC158672
0.5778	Remote Similarity	NPC608121
0.573	Remote Similarity	NPC201900
0.561	Remote Similarity	NPC487917
0.5465	Remote Similarity	NPC473262
0.5465	Remote Similarity	NPC202166
0.5444	Remote Similarity	NPC66855
0.5444	Remote Similarity	NPC181086
0.5393	Remote Similarity	NPC304257
0.5341	Remote Similarity	NPC145149
0.5341	Remote Similarity	NPC473261
0.5341	Remote Similarity	NPC300912
0.5333	Remote Similarity	NPC487872
0.5333	Remote Similarity	NPC608122
0.5312	Remote Similarity	NPC202866
0.5281	Remote Similarity	NPC313173
0.5268	Remote Similarity	NPC179896
0.5222	Remote Similarity	NPC260270
0.5165	Remote Similarity	NPC470886
0.5161	Remote Similarity	NPC487873
0.5106	Remote Similarity	NPC477220
0.5054	Remote Similarity	NPC130714

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC601097 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4678
0.1-0.2	4468
0.2-0.3	4
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