NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	260.12
Volume:	260.213
LogP:	0.62
LogD:	0.488
LogS:	-2.077
# Rotatable Bonds:	2
TPSA:	69.64
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.766
Synthetic Accessibility Score:	3.097
Fsp3:	0.429
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.209
MDCK Permeability:	1.7132488210336305e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.195
Human Intestinal Absorption (HIA):	0.09
20% Bioavailability (F20%):	0.747
30% Bioavailability (F30%):	0.937

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.242
Plasma Protein Binding (PPB):	21.57284164428711%
Volume Distribution (VD):	0.614
Pgp-substrate:	68.09175872802734%

ADMET: Metabolism

CYP1A2-inhibitor:	0.026
CYP1A2-substrate:	0.073
CYP2C19-inhibitor:	0.088
CYP2C19-substrate:	0.556
CYP2C9-inhibitor:	0.062
CYP2C9-substrate:	0.521
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.267
CYP3A4-inhibitor:	0.076
CYP3A4-substrate:	0.381

ADMET: Excretion

Clearance (CL):	4.012
Half-life (T1/2):	0.619

ADMET: Toxicity

hERG Blockers:	0.037
Human Hepatotoxicity (H-HT):	0.935
Drug-inuced Liver Injury (DILI):	0.695
AMES Toxicity:	0.025
Rat Oral Acute Toxicity:	0.298
Maximum Recommended Daily Dose:	0.934
Skin Sensitization:	0.162
Carcinogencity:	0.177
Eye Corrosion:	0.003
Eye Irritation:	0.019
Respiratory Toxicity:	0.119

Download Data

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

Natural Product: NPC175726

Natural Product ID:	NPC175726
*Common Name:**	(3S,7R,8Ar)-3-Benzyl-7-Hydroxyhexahydropyrrolo[1,2-A]Pyrazine-1,4-Dione
IUPAC Name:	(3S,7R,8aR)-3-benzyl-7-hydroxy-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:
Standard InCHIKey:	PYQJYHACQOBZLF-GRYCIOLGSA-N
Standard InCHI:	InChI=1S/C14H16N2O3/c17-10-7-12-13(18)15-11(14(19)16(12)8-10)6-9-4-2-1-3-5-9/h1-5,10-12,17H,6-8H2,(H,15,18)/t10-,11+,12-/m1/s1
SMILES:	O[C@@H]1C[C@H]2N(C1)C(=O)[C@@H](N=C2O)Cc1ccccc1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2229110
PubChem CID:	10801306
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:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

*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
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17616609]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17929896]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19113967]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19159274]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19256529]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu	2003	PMID[20303767]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21667925]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21954885]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22106303]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	stem bark of Melia azedarach	n.a.	n.a.	PMID[22409377]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23557488]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23563483]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7622436]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	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	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
Others	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT176	Organism	Artemia salina	Artemia salina	LC50	>	100.0	ug.mL-1	PMID[496391]

☑ 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 NPC175726 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	135
0.1-0.2	751
0.2-0.3	5137
0.3-0.4	21444
0.4-0.5	12004
0.5-0.6	2396
0.6-0.7	557
0.7-0.8	233
0.8-0.85	31
0.85-0.9	4
0.9-0.95	3
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC474082
0.9391	High Similarity	NPC315276
0.9391	High Similarity	NPC14672
0.9391	High Similarity	NPC285926
0.8607	High Similarity	NPC200964
0.8548	High Similarity	NPC6975
0.8468	Intermediate Similarity	NPC252878
0.8417	Intermediate Similarity	NPC33742
0.84	Intermediate Similarity	NPC46427
0.8387	Intermediate Similarity	NPC202521
0.8321	Intermediate Similarity	NPC248283
0.8306	Intermediate Similarity	NPC476990
0.8271	Intermediate Similarity	NPC178662
0.8271	Intermediate Similarity	NPC92784
0.8271	Intermediate Similarity	NPC476133
0.8271	Intermediate Similarity	NPC98424
0.8271	Intermediate Similarity	NPC470884
0.8244	Intermediate Similarity	NPC287401
0.8235	Intermediate Similarity	NPC471680
0.8154	Intermediate Similarity	NPC200589
0.8134	Intermediate Similarity	NPC242159
0.8134	Intermediate Similarity	NPC313694
0.8102	Intermediate Similarity	NPC209509
0.8092	Intermediate Similarity	NPC130309
0.8092	Intermediate Similarity	NPC255447
0.806	Intermediate Similarity	NPC471265
0.806	Intermediate Similarity	NPC471264
0.8029	Intermediate Similarity	NPC476978
0.8029	Intermediate Similarity	NPC52748
0.7939	Intermediate Similarity	NPC473322
0.792	Intermediate Similarity	NPC470545
0.7914	Intermediate Similarity	NPC262077
0.7886	Intermediate Similarity	NPC276949
0.7886	Intermediate Similarity	NPC35850
0.7883	Intermediate Similarity	NPC263493
0.7883	Intermediate Similarity	NPC269398
0.7863	Intermediate Similarity	NPC319766
0.7857	Intermediate Similarity	NPC470546
0.7842	Intermediate Similarity	NPC315266
0.7842	Intermediate Similarity	NPC5620
0.784	Intermediate Similarity	NPC470544
0.7826	Intermediate Similarity	NPC161069
0.7803	Intermediate Similarity	NPC469666
0.7803	Intermediate Similarity	NPC111428
0.7801	Intermediate Similarity	NPC471821
0.7801	Intermediate Similarity	NPC471820
0.7746	Intermediate Similarity	NPC2501
0.7717	Intermediate Similarity	NPC220698
0.7708	Intermediate Similarity	NPC122590
0.7681	Intermediate Similarity	NPC239762
0.7681	Intermediate Similarity	NPC163392
0.7676	Intermediate Similarity	NPC240848
0.7674	Intermediate Similarity	NPC71684
0.7647	Intermediate Similarity	NPC141050
0.7622	Intermediate Similarity	NPC283783
0.7622	Intermediate Similarity	NPC129666
0.7619	Intermediate Similarity	NPC297145
0.7619	Intermediate Similarity	NPC197743
0.7612	Intermediate Similarity	NPC300315
0.7606	Intermediate Similarity	NPC138775
0.7591	Intermediate Similarity	NPC118099
0.7591	Intermediate Similarity	NPC293377
0.7591	Intermediate Similarity	NPC76785
0.7591	Intermediate Similarity	NPC9687
0.7591	Intermediate Similarity	NPC151706
0.7591	Intermediate Similarity	NPC79465
0.7591	Intermediate Similarity	NPC474787
0.7591	Intermediate Similarity	NPC476102
0.7591	Intermediate Similarity	NPC273907
0.7591	Intermediate Similarity	NPC474811
0.7591	Intermediate Similarity	NPC90194
0.7591	Intermediate Similarity	NPC475598
0.7591	Intermediate Similarity	NPC474855
0.7591	Intermediate Similarity	NPC475318
0.7591	Intermediate Similarity	NPC49577
0.7591	Intermediate Similarity	NPC260045
0.7576	Intermediate Similarity	NPC101719
0.7559	Intermediate Similarity	NPC239357
0.7554	Intermediate Similarity	NPC307357
0.7554	Intermediate Similarity	NPC268841
0.7554	Intermediate Similarity	NPC46098
0.7535	Intermediate Similarity	NPC314358
0.7518	Intermediate Similarity	NPC314388
0.7518	Intermediate Similarity	NPC315283
0.7517	Intermediate Similarity	NPC162104
0.7517	Intermediate Similarity	NPC469901
0.75	Intermediate Similarity	NPC222466
0.7483	Intermediate Similarity	NPC16188
0.7465	Intermediate Similarity	NPC322878
0.7465	Intermediate Similarity	NPC316008
0.7465	Intermediate Similarity	NPC313867
0.7447	Intermediate Similarity	NPC139326
0.7429	Intermediate Similarity	NPC476259
0.7365	Intermediate Similarity	NPC476268
0.7361	Intermediate Similarity	NPC225648
0.7361	Intermediate Similarity	NPC329761
0.7361	Intermediate Similarity	NPC145113
0.7357	Intermediate Similarity	NPC89489
0.7343	Intermediate Similarity	NPC477217
0.7343	Intermediate Similarity	NPC201244
0.7333	Intermediate Similarity	NPC469898
0.7329	Intermediate Similarity	NPC7817
0.7329	Intermediate Similarity	NPC473491
0.7329	Intermediate Similarity	NPC475168
0.7328	Intermediate Similarity	NPC27833
0.7328	Intermediate Similarity	NPC302169
0.7324	Intermediate Similarity	NPC77905
0.7324	Intermediate Similarity	NPC197682
0.731	Intermediate Similarity	NPC105717
0.7286	Intermediate Similarity	NPC127741
0.7286	Intermediate Similarity	NPC68865
0.7254	Intermediate Similarity	NPC168113
0.7246	Intermediate Similarity	NPC325479
0.7241	Intermediate Similarity	NPC135121
0.7236	Intermediate Similarity	NPC473418
0.723	Intermediate Similarity	NPC202198
0.723	Intermediate Similarity	NPC262166
0.7227	Intermediate Similarity	NPC472258
0.7203	Intermediate Similarity	NPC176226
0.7185	Intermediate Similarity	NPC47667
0.7185	Intermediate Similarity	NPC474847
0.7181	Intermediate Similarity	NPC470902
0.7177	Intermediate Similarity	NPC45033
0.7165	Intermediate Similarity	NPC329011
0.7164	Intermediate Similarity	NPC35996
0.7154	Intermediate Similarity	NPC88267
0.7154	Intermediate Similarity	NPC194390
0.7154	Intermediate Similarity	NPC113326
0.7154	Intermediate Similarity	NPC224610
0.7152	Intermediate Similarity	NPC477462
0.7152	Intermediate Similarity	NPC324850
0.7134	Intermediate Similarity	NPC89831
0.7133	Intermediate Similarity	NPC469427
0.7133	Intermediate Similarity	NPC469426
0.7133	Intermediate Similarity	NPC476989
0.7124	Intermediate Similarity	NPC241794
0.7124	Intermediate Similarity	NPC73655
0.7122	Intermediate Similarity	NPC246079
0.7114	Intermediate Similarity	NPC473341
0.7114	Intermediate Similarity	NPC286551
0.7113	Intermediate Similarity	NPC132636
0.7111	Intermediate Similarity	NPC22746
0.7107	Intermediate Similarity	NPC12730
0.7099	Intermediate Similarity	NPC169328
0.7094	Intermediate Similarity	NPC226438
0.7087	Intermediate Similarity	NPC319579
0.7077	Intermediate Similarity	NPC197470
0.7075	Intermediate Similarity	NPC324445
0.7073	Intermediate Similarity	NPC164859
0.7067	Intermediate Similarity	NPC473002
0.7059	Intermediate Similarity	NPC161972
0.7059	Intermediate Similarity	NPC303045
0.7059	Intermediate Similarity	NPC474479
0.7047	Intermediate Similarity	NPC233702
0.7045	Intermediate Similarity	NPC314992
0.7045	Intermediate Similarity	NPC310467
0.7044	Intermediate Similarity	NPC136797
0.7023	Intermediate Similarity	NPC2265
0.702	Intermediate Similarity	NPC469903
0.702	Intermediate Similarity	NPC244509
0.7006	Intermediate Similarity	NPC280022
0.7006	Intermediate Similarity	NPC473000
0.7	Intermediate Similarity	NPC56685
0.7	Intermediate Similarity	NPC469900
0.6993	Remote Similarity	NPC122553
0.6993	Remote Similarity	NPC244336
0.6981	Remote Similarity	NPC137627
0.6978	Remote Similarity	NPC69496
0.6968	Remote Similarity	NPC471053
0.6968	Remote Similarity	NPC471051
0.6968	Remote Similarity	NPC471052
0.6963	Remote Similarity	NPC84281
0.6963	Remote Similarity	NPC317474
0.6963	Remote Similarity	NPC291027
0.6963	Remote Similarity	NPC169485
0.6963	Remote Similarity	NPC213126
0.6962	Remote Similarity	NPC475204
0.6962	Remote Similarity	NPC475123
0.6947	Remote Similarity	NPC188010
0.6947	Remote Similarity	NPC101139
0.6943	Remote Similarity	NPC328649
0.6943	Remote Similarity	NPC302597
0.6942	Remote Similarity	NPC311242
0.694	Remote Similarity	NPC478015
0.694	Remote Similarity	NPC478016
0.694	Remote Similarity	NPC478014
0.6937	Remote Similarity	NPC471165
0.6937	Remote Similarity	NPC26108
0.6923	Remote Similarity	NPC63931
0.6917	Remote Similarity	NPC256452
0.6914	Remote Similarity	NPC97526
0.6914	Remote Similarity	NPC119652
0.6905	Remote Similarity	NPC474804
0.6905	Remote Similarity	NPC474973
0.6905	Remote Similarity	NPC327481
0.6905	Remote Similarity	NPC130898
0.6892	Remote Similarity	NPC311658
0.6887	Remote Similarity	NPC5194
0.6887	Remote Similarity	NPC261934
0.6885	Remote Similarity	NPC322598

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 NPC175726 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	103
0.1-0.2	342
0.2-0.3	674
0.3-0.4	2235
0.4-0.5	3767
0.5-0.6	1617
0.6-0.7	354
0.7-0.8	53
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.84	Intermediate Similarity	NPD2584	Suspended
0.8333	Intermediate Similarity	NPD8173	Phase 2
0.8333	Intermediate Similarity	NPD8172	Phase 2
0.8281	Intermediate Similarity	NPD5339	Clinical (unspecified phase)
0.8258	Intermediate Similarity	NPD7113	Clinical (unspecified phase)
0.7926	Intermediate Similarity	NPD4782	Clinical (unspecified phase)
0.7895	Intermediate Similarity	NPD3632	Clinical (unspecified phase)
0.7846	Intermediate Similarity	NPD6792	Phase 3
0.7803	Intermediate Similarity	NPD3626	Phase 3
0.7786	Intermediate Similarity	NPD2585	Clinical (unspecified phase)
0.7778	Intermediate Similarity	NPD4791	Clinical (unspecified phase)
0.7744	Intermediate Similarity	NPD4125	Approved
0.7727	Intermediate Similarity	NPD3604	Clinical (unspecified phase)
0.7714	Intermediate Similarity	NPD6860	Clinical (unspecified phase)
0.7704	Intermediate Similarity	NPD941	Approved
0.7647	Intermediate Similarity	NPD8416	Discontinued
0.7639	Intermediate Similarity	NPD7613	Discontinued
0.7619	Intermediate Similarity	NPD7118	Clinical (unspecified phase)
0.7615	Intermediate Similarity	NPD4762	Approved
0.7615	Intermediate Similarity	NPD4761	Approved
0.7606	Intermediate Similarity	NPD8323	Discontinued
0.7576	Intermediate Similarity	NPD2031	Discontinued
0.7557	Intermediate Similarity	NPD3072	Approved
0.7557	Intermediate Similarity	NPD3071	Approved
0.7557	Intermediate Similarity	NPD3073	Approved
0.7537	Intermediate Similarity	NPD4175	Approved
0.7537	Intermediate Similarity	NPD4177	Approved
0.7521	Intermediate Similarity	NPD999	Phase 2
0.7518	Intermediate Similarity	NPD5341	Clinical (unspecified phase)
0.7482	Intermediate Similarity	NPD6901	Phase 3
0.7481	Intermediate Similarity	NPD4706	Clinical (unspecified phase)
0.7463	Intermediate Similarity	NPD3588	Discontinued
0.7353	Intermediate Similarity	NPD5263	Approved
0.7338	Intermediate Similarity	NPD3577	Discontinued
0.7338	Intermediate Similarity	NPD8643	Discontinued
0.7333	Intermediate Similarity	NPD3608	Clinical (unspecified phase)
0.7317	Intermediate Similarity	NPD7130	Phase 3
0.7305	Intermediate Similarity	NPD7728	Clinical (unspecified phase)
0.7299	Intermediate Similarity	NPD4794	Discontinued
0.7286	Intermediate Similarity	NPD6073	Approved
0.7252	Intermediate Similarity	NPD4504	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD2078	Clinical (unspecified phase)
0.7246	Intermediate Similarity	NPD1330	Phase 2
0.7246	Intermediate Similarity	NPD1329	Clinical (unspecified phase)
0.7244	Intermediate Similarity	NPD480	Approved
0.7226	Intermediate Similarity	NPD4676	Approved
0.7226	Intermediate Similarity	NPD7979	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD7267	Clinical (unspecified phase)
0.7163	Intermediate Similarity	NPD5725	Approved
0.7153	Intermediate Similarity	NPD3040	Approved
0.7143	Intermediate Similarity	NPD6631	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD4153	Approved
0.7143	Intermediate Similarity	NPD3581	Discontinued
0.7113	Intermediate Similarity	NPD6852	Discontinued
0.7105	Intermediate Similarity	NPD7011	Discontinued
0.7092	Intermediate Similarity	NPD3908	Approved
0.7083	Intermediate Similarity	NPD8076	Discontinued
0.7083	Intermediate Similarity	NPD4152	Approved
0.7077	Intermediate Similarity	NPD1348	Approved
0.7071	Intermediate Similarity	NPD3561	Clinical (unspecified phase)
0.7045	Intermediate Similarity	NPD2217	Approved
0.7045	Intermediate Similarity	NPD2218	Phase 2
0.7045	Intermediate Similarity	NPD6343	Approved
0.7045	Intermediate Similarity	NPD998	Approved
0.7045	Intermediate Similarity	NPD6345	Approved
0.7029	Intermediate Similarity	NPD5759	Approved
0.7023	Intermediate Similarity	NPD3123	Discovery
0.6985	Remote Similarity	NPD4677	Discontinued
0.6981	Remote Similarity	NPD7964	Clinical (unspecified phase)
0.6981	Remote Similarity	NPD7965	Phase 2
0.698	Remote Similarity	NPD979	Approved
0.6978	Remote Similarity	NPD2613	Approved
0.6972	Remote Similarity	NPD4757	Clinical (unspecified phase)
0.6966	Remote Similarity	NPD7720	Phase 2
0.6963	Remote Similarity	NPD4215	Approved
0.6963	Remote Similarity	NPD2612	Approved
0.6963	Remote Similarity	NPD4218	Approved
0.6963	Remote Similarity	NPD2611	Approved
0.6963	Remote Similarity	NPD2608	Approved
0.6963	Remote Similarity	NPD2609	Approved
0.6963	Remote Similarity	NPD3132	Approved
0.6963	Remote Similarity	NPD3131	Approved
0.6963	Remote Similarity	NPD2610	Approved
0.6963	Remote Similarity	NPD4217	Approved
0.6963	Remote Similarity	NPD4216	Approved
0.696	Remote Similarity	NPD1018	Approved
0.6957	Remote Similarity	NPD4151	Approved
0.6953	Remote Similarity	NPD3642	Approved
0.6953	Remote Similarity	NPD3643	Approved
0.6953	Remote Similarity	NPD3644	Approved
0.695	Remote Similarity	NPD7634	Clinical (unspecified phase)
0.695	Remote Similarity	NPD5747	Discontinued
0.6944	Remote Similarity	NPD5301	Clinical (unspecified phase)
0.6939	Remote Similarity	NPD6676	Phase 2
0.6939	Remote Similarity	NPD1968	Approved
0.6939	Remote Similarity	NPD1967	Approved
0.6934	Remote Similarity	NPD3125	Approved
0.6934	Remote Similarity	NPD5577	Clinical (unspecified phase)
0.6934	Remote Similarity	NPD5578	Approved
0.6934	Remote Similarity	NPD2634	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD2048	Approved
0.6929	Remote Similarity	NPD2045	Approved
0.6929	Remote Similarity	NPD2044	Approved
0.6929	Remote Similarity	NPD2047	Approved
0.6929	Remote Similarity	NPD2051	Approved
0.6929	Remote Similarity	NPD21	Approved
0.6929	Remote Similarity	NPD2046	Approved
0.6929	Remote Similarity	NPD2049	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD6919	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD2050	Clinical (unspecified phase)
0.6929	Remote Similarity	NPD2043	Approved
0.6923	Remote Similarity	NPD3598	Phase 3
0.6901	Remote Similarity	NPD6623	Phase 3
0.6901	Remote Similarity	NPD5296	Approved
0.6894	Remote Similarity	NPD1344	Phase 2
0.6879	Remote Similarity	NPD5299	Approved
0.6875	Remote Similarity	NPD4126	Approved
0.6871	Remote Similarity	NPD5265	Approved
0.6871	Remote Similarity	NPD5264	Approved
0.6863	Remote Similarity	NPD8417	Discontinued
0.6849	Remote Similarity	NPD2087	Approved
0.6849	Remote Similarity	NPD2088	Approved
0.6849	Remote Similarity	NPD2022	Approved
0.6846	Remote Similarity	NPD8290	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD5991	Approved
0.6842	Remote Similarity	NPD5990	Approved
0.6842	Remote Similarity	NPD7522	Discontinued
0.6842	Remote Similarity	NPD3806	Clinical (unspecified phase)
0.6831	Remote Similarity	NPD2570	Approved
0.6831	Remote Similarity	NPD2573	Approved
0.6831	Remote Similarity	NPD3615	Approved
0.6831	Remote Similarity	NPD4745	Approved
0.6831	Remote Similarity	NPD3088	Approved
0.6831	Remote Similarity	NPD3087	Approved
0.6831	Remote Similarity	NPD3090	Approved
0.6831	Remote Similarity	NPD4746	Phase 3
0.6831	Remote Similarity	NPD2571	Approved
0.6831	Remote Similarity	NPD2572	Clinical (unspecified phase)
0.6831	Remote Similarity	NPD3616	Approved
0.6831	Remote Similarity	NPD2566	Approved
0.6831	Remote Similarity	NPD3089	Approved
0.6831	Remote Similarity	NPD2574	Discontinued
0.6831	Remote Similarity	NPD3614	Approved
0.6822	Remote Similarity	NPD2583	Phase 2
0.6821	Remote Similarity	NPD6144	Discontinued
0.6809	Remote Similarity	NPD4738	Phase 2
0.6803	Remote Similarity	NPD2436	Approved
0.6803	Remote Similarity	NPD2437	Approved
0.68	Remote Similarity	NPD3282	Phase 1
0.68	Remote Similarity	NPD7892	Clinical (unspecified phase)
0.68	Remote Similarity	NPD3283	Phase 3
0.68	Remote Similarity	NPD6088	Approved
0.6783	Remote Similarity	NPD5323	Approved
0.6781	Remote Similarity	NPD7511	Approved
0.6781	Remote Similarity	NPD7512	Approved
0.6779	Remote Similarity	NPD7602	Clinical (unspecified phase)
0.6779	Remote Similarity	NPD6552	Clinical (unspecified phase)
0.6776	Remote Similarity	NPD7131	Phase 3
0.6769	Remote Similarity	NPD753	Approved
0.6763	Remote Similarity	NPD2160	Approved
0.6763	Remote Similarity	NPD2627	Approved
0.6763	Remote Similarity	NPD2159	Approved
0.6763	Remote Similarity	NPD3029	Clinical (unspecified phase)
0.6763	Remote Similarity	NPD2626	Approved
0.6763	Remote Similarity	NPD2628	Approved
0.6763	Remote Similarity	NPD2625	Approved
0.6761	Remote Similarity	NPD5581	Approved
0.6759	Remote Similarity	NPD6294	Approved
0.6759	Remote Similarity	NPD6295	Approved
0.6748	Remote Similarity	NPD466	Approved
0.6742	Remote Similarity	NPD3551	Approved
0.6742	Remote Similarity	NPD1711	Phase 2
0.6742	Remote Similarity	NPD747	Discontinued
0.6736	Remote Similarity	NPD4684	Phase 3
0.6736	Remote Similarity	NPD4685	Phase 3
0.6736	Remote Similarity	NPD4686	Approved
0.6732	Remote Similarity	NPD8315	Phase 1
0.672	Remote Similarity	NPD854	Approved
0.672	Remote Similarity	NPD855	Approved
0.6712	Remote Similarity	NPD3480	Approved
0.671	Remote Similarity	NPD951	Approved
0.6708	Remote Similarity	NPD5137	Approved
0.6694	Remote Similarity	NPD742	Approved
0.6691	Remote Similarity	NPD7342	Discontinued
0.6691	Remote Similarity	NPD6325	Discontinued
0.669	Remote Similarity	NPD4497	Clinical (unspecified phase)
0.6689	Remote Similarity	NPD5614	Approved
0.6689	Remote Similarity	NPD5613	Approved
0.6667	Remote Similarity	NPD8126	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD6408	Phase 1
0.6667	Remote Similarity	NPD478	Approved
0.6667	Remote Similarity	NPD8265	Approved
0.6667	Remote Similarity	NPD8124	Phase 3
0.6667	Remote Similarity	NPD5108	Clinical (unspecified phase)
0.6646	Remote Similarity	NPD5681	Clinical (unspecified phase)
0.6645	Remote Similarity	NPD4432	Discontinued
0.6643	Remote Similarity	NPD4619	Approved
0.6643	Remote Similarity	NPD4621	Approved
0.6642	Remote Similarity	NPD5187	Clinical (unspecified phase)
0.6624	Remote Similarity	NPD7599	Phase 2

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