NPASS Compound

Structure

NPC473495 OpenBabel07101718202D 48 47 0 0 1 0 0 0 0 0999 V2000 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6603 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9282 -2.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4641 -2.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9282 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5981 2.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.0622 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 4.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 S 0 0 3 0 0 0 0 0 0 0 0 0 1 16 1 0 0 0 0 2 17 1 0 0 0 0 3 20 1 0 0 0 0 4 20 1 0 0 0 0 5 21 1 0 0 0 0 6 21 1 0 0 0 0 10 35 1 0 0 0 0 11 37 1 0 0 0 0 12 38 1 0 0 0 0 13 39 1 0 0 0 0 14 40 1 0 0 0 0 15 48 1 0 0 0 0 16 22 1 0 0 0 0 17 23 1 0 0 0 0 18 19 2 0 0 0 0 18 25 1 0 0 0 0 19 48 1 0 0 0 0 22 7 1 6 0 0 0 22 28 1 0 0 0 0 23 8 1 1 0 0 0 23 29 1 0 0 0 0 24 9 1 6 0 0 0 24 32 1 0 0 0 0 24 37 1 0 0 0 0 25 37 1 0 0 0 0 25 41 2 0 0 0 0 26 20 1 6 0 0 0 26 33 1 0 0 0 0 26 36 1 0 0 0 0 27 21 1 6 0 0 0 27 31 1 0 0 0 0 27 38 1 0 0 0 0 28 30 1 1 0 0 0 28 39 1 0 0 0 0 29 34 1 6 0 0 0 29 40 1 0 0 0 0 30 35 2 3 0 0 0 30 42 1 0 0 0 0 31 36 2 3 0 0 0 31 43 1 0 0 0 0 32 40 1 0 0 0 0 32 44 2 0 0 0 0 33 39 1 0 0 0 0 33 45 2 0 0 0 0 34 38 1 0 0 0 0 34 46 2 0 0 0 0 47 48 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	698.44
Volume:	724.186
LogP:	2.043
LogD:	0.986
LogS:	-3.335
# Rotatable Bonds:	24
TPSA:	162.5
# H-Bond Aceptor:	13
# H-Bond Donor:	2
# Rings:	0
# Heavy Atoms:	14

MedChem Properties

QED Drug-Likeness Score:	0.163
Synthetic Accessibility Score:	5.308
Fsp3:	0.765
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.221
MDCK Permeability:	7.835897122276947e-06
Pgp-inhibitor:	0.999
Pgp-substrate:	0.973
Human Intestinal Absorption (HIA):	0.955
20% Bioavailability (F20%):	0.352
30% Bioavailability (F30%):	0.165

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.081
Plasma Protein Binding (PPB):	73.32122039794922%
Volume Distribution (VD):	0.705
Pgp-substrate:	22.485031127929688%

ADMET: Metabolism

CYP1A2-inhibitor:	0.0
CYP1A2-substrate:	0.058
CYP2C19-inhibitor:	0.027
CYP2C19-substrate:	0.798
CYP2C9-inhibitor:	0.066
CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.073
CYP3A4-inhibitor:	0.453
CYP3A4-substrate:	0.889

ADMET: Excretion

Clearance (CL):	4.437
Half-life (T1/2):	0.699

ADMET: Toxicity

hERG Blockers:	0.001
Human Hepatotoxicity (H-HT):	0.862
Drug-inuced Liver Injury (DILI):	0.962
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.053
Maximum Recommended Daily Dose:	0.023
Skin Sensitization:	0.092
Carcinogencity:	0.016
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.049

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC473495

Natural Product ID:	NPC473495
*Common Name:**	Pterulamide I
IUPAC Name:	(2S,3S)-N,3-dimethyl-2-[methyl-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-[methyl-[(2S,3S)-3-methyl-2-[methyl-[(2S)-2-[methyl-[(E)-3-methylsulfinylprop-2-enoyl]amino]propanoyl]amino]pentanoyl]amino]butanoyl]amino]butanoyl]amino]pentanamide
Synonyms:	pterulamide I
Standard InCHIKey:	VJHQQCCKXFLKLU-QZFMFPMKSA-N
Standard InCHI:	InChI=1S/C34H62N6O7S/c1-16-22(7)28(30(42)35-10)39(13)33(45)26(20(3)4)36-31(43)27(21(5)6)38(12)34(46)29(23(8)17-2)40(14)32(44)24(9)37(11)25(41)18-19-48(15)47/h18-24,26-29H,16-17H2,1-15H3,(H,35,42)(H,36,43)/b19-18+/t22-,23-,24-,26-,27-,28-,29-,48?/m0/s1
SMILES:	CC[C@@H]([C@H](N(C(=O)[C@@H](N(C(=O)/C=C/S(=O)C)C)C)C)C(=O)N([C@H](C(=N[C@H](C(=O)N([C@H](C(=NC)O)[C@H](CC)C)C)C(C)C)O)C(C)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL443715
PubChem CID:	16091506
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33341	pterula sp.	Species	Pterulaceae	Eukaryota	n.a.	Malaysian	n.a.	PMID[17067148]

☑ 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	NP ID	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
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	IC50	=	790.0	nM	PMID[556090]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC473495 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	71
0.1-0.2	17036
0.2-0.3	21131
0.3-0.4	3212
0.4-0.5	950
0.5-0.6	237
0.6-0.7	53
0.7-0.8	6
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.7333	Intermediate Similarity	NPC6902
0.7333	Intermediate Similarity	NPC184473
0.7333	Intermediate Similarity	NPC284456
0.7158	Intermediate Similarity	NPC155230
0.7143	Intermediate Similarity	NPC53858
0.7143	Intermediate Similarity	NPC84128
0.6989	Remote Similarity	NPC472351
0.6739	Remote Similarity	NPC476117
0.6739	Remote Similarity	NPC476243
0.6739	Remote Similarity	NPC476156
0.6739	Remote Similarity	NPC476137
0.67	Remote Similarity	NPC38172
0.6667	Remote Similarity	NPC23984
0.6667	Remote Similarity	NPC476302
0.663	Remote Similarity	NPC31756
0.6629	Remote Similarity	NPC209156
0.6526	Remote Similarity	NPC235078
0.6509	Remote Similarity	NPC471097
0.6509	Remote Similarity	NPC475149
0.6444	Remote Similarity	NPC161774
0.6444	Remote Similarity	NPC256312
0.6444	Remote Similarity	NPC266888
0.6408	Remote Similarity	NPC469739
0.6404	Remote Similarity	NPC196007
0.6404	Remote Similarity	NPC76297
0.6404	Remote Similarity	NPC214532
0.6364	Remote Similarity	NPC171734
0.6364	Remote Similarity	NPC207820
0.6321	Remote Similarity	NPC475791
0.6321	Remote Similarity	NPC13175
0.6293	Remote Similarity	NPC239357
0.6275	Remote Similarity	NPC471098
0.6275	Remote Similarity	NPC173763
0.6275	Remote Similarity	NPC62263
0.6261	Remote Similarity	NPC473819
0.625	Remote Similarity	NPC117829
0.6226	Remote Similarity	NPC475758
0.619	Remote Similarity	NPC144780
0.6176	Remote Similarity	NPC474576
0.6174	Remote Similarity	NPC472536
0.6174	Remote Similarity	NPC103391
0.6162	Remote Similarity	NPC477539
0.6154	Remote Similarity	NPC280066
0.6147	Remote Similarity	NPC476877
0.6105	Remote Similarity	NPC312315
0.6078	Remote Similarity	NPC474593
0.6078	Remote Similarity	NPC475801
0.6075	Remote Similarity	NPC220234
0.6071	Remote Similarity	NPC296143
0.6058	Remote Similarity	NPC301010
0.6038	Remote Similarity	NPC473597
0.6036	Remote Similarity	NPC476876
0.5979	Remote Similarity	NPC470783
0.5966	Remote Similarity	NPC469899
0.5909	Remote Similarity	NPC124554
0.5909	Remote Similarity	NPC5864
0.5909	Remote Similarity	NPC301148
0.5888	Remote Similarity	NPC134504
0.5888	Remote Similarity	NPC47076
0.5865	Remote Similarity	NPC477538
0.5851	Remote Similarity	NPC477863
0.5843	Remote Similarity	NPC84182
0.5843	Remote Similarity	NPC128005
0.5804	Remote Similarity	NPC323720
0.5804	Remote Similarity	NPC124549
0.5781	Remote Similarity	NPC300315
0.578	Remote Similarity	NPC475440
0.5776	Remote Similarity	NPC476875
0.5758	Remote Similarity	NPC246005
0.5752	Remote Similarity	NPC241394
0.5745	Remote Similarity	NPC477862
0.5729	Remote Similarity	NPC59867
0.5714	Remote Similarity	NPC306696
0.5714	Remote Similarity	NPC288109
0.5714	Remote Similarity	NPC250953
0.5714	Remote Similarity	NPC296043
0.5714	Remote Similarity	NPC198344
0.5714	Remote Similarity	NPC47230
0.5714	Remote Similarity	NPC17143
0.5714	Remote Similarity	NPC89489
0.5684	Remote Similarity	NPC327272
0.5667	Remote Similarity	NPC329216
0.5664	Remote Similarity	NPC128303
0.566	Remote Similarity	NPC315237
0.5657	Remote Similarity	NPC475542
0.5656	Remote Similarity	NPC470546
0.5652	Remote Similarity	NPC67009
0.5638	Remote Similarity	NPC315897
0.5635	Remote Similarity	NPC22746
0.562	Remote Similarity	NPC322878
0.5614	Remote Similarity	NPC475637
0.561	Remote Similarity	NPC315188
0.561	Remote Similarity	NPC160688

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473495 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	64
0.1-0.2	1279
0.2-0.3	5688
0.3-0.4	1677
0.4-0.5	361
0.5-0.6	69
0.6-0.7	12
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
0.7033	Intermediate Similarity	NPD7762	Phase 2
0.7033	Intermediate Similarity	NPD7763	Phase 2
0.6667	Remote Similarity	NPD5791	Phase 2
0.663	Remote Similarity	NPD4815	Discontinued
0.65	Remote Similarity	NPD5792	Clinical (unspecified phase)
0.6495	Remote Similarity	NPD7760	Phase 2
0.6495	Remote Similarity	NPD7759	Phase 2
0.6458	Remote Similarity	NPD3733	Clinical (unspecified phase)
0.6422	Remote Similarity	NPD2147	Approved
0.6421	Remote Similarity	NPD2683	Discontinued
0.6289	Remote Similarity	NPD9577	Approved
0.6168	Remote Similarity	NPD6120	Clinical (unspecified phase)
0.6162	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.6038	Remote Similarity	NPD1784	Approved
0.6	Remote Similarity	NPD620	Approved
0.6	Remote Similarity	NPD2090	Approved
0.5981	Remote Similarity	NPD8038	Phase 2
0.5943	Remote Similarity	NPD7841	Clinical (unspecified phase)
0.5935	Remote Similarity	NPD8041	Phase 2
0.5934	Remote Similarity	NPD9649	Approved
0.578	Remote Similarity	NPD4825	Clinical (unspecified phase)
0.5778	Remote Similarity	NPD9666	Clinical (unspecified phase)
0.5778	Remote Similarity	NPD9665	Clinical (unspecified phase)
0.5758	Remote Similarity	NPD1125	Discovery
0.575	Remote Similarity	NPD2099	Approved
0.5728	Remote Similarity	NPD3177	Phase 3
0.5714	Remote Similarity	NPD322	Phase 1
0.5714	Remote Similarity	NPD4261	Phase 1
0.5714	Remote Similarity	NPD9578	Clinical (unspecified phase)
0.57	Remote Similarity	NPD7643	Phase 1
0.566	Remote Similarity	NPD6699	Clinical (unspecified phase)
0.5638	Remote Similarity	NPD266	Phase 3
0.5638	Remote Similarity	NPD1825	Clinical (unspecified phase)
0.5638	Remote Similarity	NPD265	Phase 3
0.563	Remote Similarity	NPD2100	Approved
0.5619	Remote Similarity	NPD1782	Approved

Bioactivity similarity: Similar Natural Products in NPASS

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