NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	336.16
Volume:	343.3
LogP:	0.971
LogD:	0.911
LogS:	-1.183
# Rotatable Bonds:	0
TPSA:	27.69
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.69
Synthetic Accessibility Score:	4.769
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:	-5.461
MDCK Permeability:	2.4475844838889316e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.999
Human Intestinal Absorption (HIA):	0.75
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.271
Plasma Protein Binding (PPB):	30.470848083496094%
Volume Distribution (VD):	2.522
Pgp-substrate:	59.41270446777344%

ADMET: Metabolism

CYP1A2-inhibitor:	0.367
CYP1A2-substrate:	0.931
CYP2C19-inhibitor:	0.226
CYP2C19-substrate:	0.206
CYP2C9-inhibitor:	0.007
CYP2C9-substrate:	0.061
CYP2D6-inhibitor:	0.166
CYP2D6-substrate:	0.923
CYP3A4-inhibitor:	0.499
CYP3A4-substrate:	0.854

ADMET: Excretion

Clearance (CL):	2.509
Half-life (T1/2):	0.833

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.037
Drug-inuced Liver Injury (DILI):	0.034
AMES Toxicity:	0.2
Rat Oral Acute Toxicity:	0.692
Maximum Recommended Daily Dose:	0.999
Skin Sensitization:	0.042
Carcinogencity:	0.959
Eye Corrosion:	0.003
Eye Irritation:	0.049
Respiratory Toxicity:	0.23

Download Data

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

Natural Product: NPC477080

Natural Product ID:	NPC477080
*Common Name:**	(1S,12S)-23,23-dimethyl-5,7,17-trioxa-23-azoniahexacyclo[10.10.1.02,10.04,8.013,21.015,19]tricosa-2,4(8),9,13,15(19),20-hexaene;chloride
IUPAC Name:	(1S,12S)-23,23-dimethyl-5,7,17-trioxa-23-azoniahexacyclo[10.10.1.02,10.04,8.013,21.015,19]tricosa-2,4(8),9,13,15(19),20-hexaene;chloride
Synonyms:	Californidine
Standard InCHIKey:	GLCGPUDWOPXBAY-HLRBRJAUSA-M
Standard InCHI:	InChI=1S/C21H22NO3.ClH/c1-22(2)18-6-13-7-20-21(25-11-24-20)8-17(13)19(22)5-12-3-14-9-23-10-15(14)4-16(12)18;/h3-4,7-8,18-19H,5-6,9-11H2,1-2H3;1H/q+1;/p-1/t18-,19-;/m0./s1
SMILES:	C[N+]1([C@H]2CC3=CC4=C(COC4)C=C3[C@@H]1CC5=CC6=C(C=C25)OCO6)C.[Cl-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	45266443
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002793] Pavine alkaloids

*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
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	Oakham, MA, US	n.a.	PMID[16562853]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17250743]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4986	Eschscholzia californica	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4986	Eschscholzia californica	Species	Papaveraceae	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
EC50	1
IC50	1

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT109	Individual Protein	Cytochrome P450 3A4	Homo sapiens	IC50	>	80000	nM	PMID[16562853]
NPT92	Individual Protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	EC50	>	100000	nM	PMID[16562853]

☑ 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 NPC477080 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	309
0.1-0.2	1549
0.2-0.3	7662
0.3-0.4	10576
0.4-0.5	7510
0.5-0.6	11505
0.6-0.7	2715
0.7-0.8	569
0.8-0.85	212
0.85-0.9	73
0.9-0.95	16
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.953	High Similarity	NPC210148
0.953	High Similarity	NPC233029
0.9216	High Similarity	NPC234392
0.9216	High Similarity	NPC31311
0.915	High Similarity	NPC138487
0.915	High Similarity	NPC216459
0.915	High Similarity	NPC41178
0.915	High Similarity	NPC76079
0.9133	High Similarity	NPC475959
0.9091	High Similarity	NPC146288
0.9038	High Similarity	NPC232924
0.9038	High Similarity	NPC477559
0.9038	High Similarity	NPC266753
0.9038	High Similarity	NPC160298
0.9038	High Similarity	NPC306902
0.8994	High Similarity	NPC210918
0.8974	High Similarity	NPC111485
0.8926	High Similarity	NPC136860
0.8926	High Similarity	NPC128019
0.8926	High Similarity	NPC476567
0.8903	High Similarity	NPC78733
0.8868	High Similarity	NPC225774
0.8868	High Similarity	NPC167546
0.8868	High Similarity	NPC302527
0.8868	High Similarity	NPC16805
0.8824	High Similarity	NPC92541
0.8824	High Similarity	NPC219162
0.8812	High Similarity	NPC476432
0.8812	High Similarity	NPC24264
0.8812	High Similarity	NPC219341
0.8774	High Similarity	NPC148898
0.8758	High Similarity	NPC247389
0.8758	High Similarity	NPC130941
0.8758	High Similarity	NPC298979
0.875	High Similarity	NPC276944
0.875	High Similarity	NPC232514
0.875	High Similarity	NPC238530
0.8725	High Similarity	NPC314682
0.8704	High Similarity	NPC241055
0.8696	High Similarity	NPC304659
0.8696	High Similarity	NPC86144
0.8693	High Similarity	NPC90844
0.8693	High Similarity	NPC95075
0.8693	High Similarity	NPC144863
0.8693	High Similarity	NPC51957
0.8693	High Similarity	NPC253883
0.8693	High Similarity	NPC210437
0.8693	High Similarity	NPC106295
0.8693	High Similarity	NPC476144
0.8693	High Similarity	NPC16107
0.8667	High Similarity	NPC328750
0.8667	High Similarity	NPC213206
0.8667	High Similarity	NPC188163
0.8667	High Similarity	NPC474915
0.8649	High Similarity	NPC7018
0.8645	High Similarity	NPC223125
0.8642	High Similarity	NPC474324
0.8642	High Similarity	NPC57812
0.8636	High Similarity	NPC7467
0.8634	High Similarity	NPC168409
0.8614	High Similarity	NPC148693
0.8614	High Similarity	NPC118633
0.8614	High Similarity	NPC294790
0.8598	High Similarity	NPC149090
0.8598	High Similarity	NPC19520
0.859	High Similarity	NPC326316
0.859	High Similarity	NPC81733
0.8589	High Similarity	NPC475845
0.8571	High Similarity	NPC189470
0.8571	High Similarity	NPC320104
0.8562	High Similarity	NPC97072
0.8562	High Similarity	NPC215829
0.8545	High Similarity	NPC2314
0.8544	High Similarity	NPC93593
0.8537	High Similarity	NPC474708
0.8537	High Similarity	NPC6152
0.8535	High Similarity	NPC223124
0.8526	High Similarity	NPC151895
0.8526	High Similarity	NPC192768
0.8526	High Similarity	NPC88249
0.8526	High Similarity	NPC97221
0.8526	High Similarity	NPC220858
0.8519	High Similarity	NPC247972
0.85	High Similarity	NPC106786
0.8494	Intermediate Similarity	NPC229166
0.8494	Intermediate Similarity	NPC199465
0.8494	Intermediate Similarity	NPC128560
0.8485	Intermediate Similarity	NPC65403
0.8457	Intermediate Similarity	NPC233650
0.8457	Intermediate Similarity	NPC59567
0.8452	Intermediate Similarity	NPC126284
0.8443	Intermediate Similarity	NPC287588
0.8442	Intermediate Similarity	NPC145304
0.8442	Intermediate Similarity	NPC185838
0.8428	Intermediate Similarity	NPC325871
0.8428	Intermediate Similarity	NPC244112
0.8428	Intermediate Similarity	NPC99659
0.8418	Intermediate Similarity	NPC26601
0.8415	Intermediate Similarity	NPC181653
0.8415	Intermediate Similarity	NPC100566
0.8415	Intermediate Similarity	NPC190332
0.8405	Intermediate Similarity	NPC134858
0.8393	Intermediate Similarity	NPC320223
0.8393	Intermediate Similarity	NPC114364
0.8383	Intermediate Similarity	NPC304675
0.8375	Intermediate Similarity	NPC247639
0.8375	Intermediate Similarity	NPC25084
0.8375	Intermediate Similarity	NPC186063
0.8364	Intermediate Similarity	NPC82533
0.8364	Intermediate Similarity	NPC266176
0.8364	Intermediate Similarity	NPC290759
0.8364	Intermediate Similarity	NPC158148
0.8353	Intermediate Similarity	NPC248642
0.8343	Intermediate Similarity	NPC267408
0.8333	Intermediate Similarity	NPC321505
0.8333	Intermediate Similarity	NPC191376
0.8333	Intermediate Similarity	NPC302001
0.8333	Intermediate Similarity	NPC179825
0.8333	Intermediate Similarity	NPC237044
0.8323	Intermediate Similarity	NPC130926
0.8323	Intermediate Similarity	NPC476572
0.8313	Intermediate Similarity	NPC187022
0.8313	Intermediate Similarity	NPC204828
0.8313	Intermediate Similarity	NPC127674
0.8313	Intermediate Similarity	NPC184026
0.8313	Intermediate Similarity	NPC249797
0.8313	Intermediate Similarity	NPC295691
0.8313	Intermediate Similarity	NPC80129
0.8313	Intermediate Similarity	NPC311991
0.8313	Intermediate Similarity	NPC193949
0.8313	Intermediate Similarity	NPC152212
0.8313	Intermediate Similarity	NPC276588
0.8313	Intermediate Similarity	NPC207757
0.8313	Intermediate Similarity	NPC278799
0.8313	Intermediate Similarity	NPC75958
0.8313	Intermediate Similarity	NPC39701
0.8313	Intermediate Similarity	NPC5238
0.8313	Intermediate Similarity	NPC469817
0.8313	Intermediate Similarity	NPC172765
0.8313	Intermediate Similarity	NPC110416
0.8313	Intermediate Similarity	NPC189266
0.8313	Intermediate Similarity	NPC54379
0.8313	Intermediate Similarity	NPC2413
0.8304	Intermediate Similarity	NPC156576
0.8303	Intermediate Similarity	NPC150879
0.8303	Intermediate Similarity	NPC210140
0.8294	Intermediate Similarity	NPC179704
0.8293	Intermediate Similarity	NPC231198
0.8284	Intermediate Similarity	NPC474325
0.828	Intermediate Similarity	NPC476571
0.828	Intermediate Similarity	NPC147390
0.828	Intermediate Similarity	NPC428
0.828	Intermediate Similarity	NPC135538
0.828	Intermediate Similarity	NPC246587
0.828	Intermediate Similarity	NPC24233
0.8266	Intermediate Similarity	NPC237579
0.8263	Intermediate Similarity	NPC470739
0.8263	Intermediate Similarity	NPC477640
0.8263	Intermediate Similarity	NPC225597
0.8261	Intermediate Similarity	NPC203784
0.8261	Intermediate Similarity	NPC126519
0.8261	Intermediate Similarity	NPC170503
0.8253	Intermediate Similarity	NPC58766
0.8253	Intermediate Similarity	NPC475686
0.8246	Intermediate Similarity	NPC299990
0.8246	Intermediate Similarity	NPC73492
0.8246	Intermediate Similarity	NPC275132
0.8246	Intermediate Similarity	NPC116284
0.8243	Intermediate Similarity	NPC160193
0.8239	Intermediate Similarity	NPC476568
0.8235	Intermediate Similarity	NPC470879
0.8235	Intermediate Similarity	NPC258695
0.8235	Intermediate Similarity	NPC474745
0.8228	Intermediate Similarity	NPC211296
0.8225	Intermediate Similarity	NPC474470
0.8225	Intermediate Similarity	NPC112575
0.8221	Intermediate Similarity	NPC166014
0.8221	Intermediate Similarity	NPC27410
0.8217	Intermediate Similarity	NPC476151
0.8204	Intermediate Similarity	NPC474475
0.8187	Intermediate Similarity	NPC474506
0.8187	Intermediate Similarity	NPC477561
0.8187	Intermediate Similarity	NPC312918
0.8187	Intermediate Similarity	NPC476574
0.8187	Intermediate Similarity	NPC32413
0.8187	Intermediate Similarity	NPC155442
0.8182	Intermediate Similarity	NPC169743
0.8182	Intermediate Similarity	NPC470925
0.8176	Intermediate Similarity	NPC23219
0.8176	Intermediate Similarity	NPC15919
0.8171	Intermediate Similarity	NPC24954
0.8166	Intermediate Similarity	NPC187678
0.8166	Intermediate Similarity	NPC477558
0.816	Intermediate Similarity	NPC216816
0.8148	Intermediate Similarity	NPC180756
0.8148	Intermediate Similarity	NPC323443
0.814	Intermediate Similarity	NPC249405
0.8125	Intermediate Similarity	NPC476579
0.8121	Intermediate Similarity	NPC475393
0.8121	Intermediate Similarity	NPC324144

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 NPC477080 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	207
0.1-0.2	748
0.2-0.3	1026
0.3-0.4	2058
0.4-0.5	2671
0.5-0.6	1711
0.6-0.7	585
0.7-0.8	129
0.8-0.85	13
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8693	High Similarity	NPD4584	Approved
0.8667	High Similarity	NPD4664	Clinical (unspecified phase)
0.8377	Intermediate Similarity	NPD5084	Clinical (unspecified phase)
0.8323	Intermediate Similarity	NPD6783	Clinical (unspecified phase)
0.8313	Intermediate Similarity	NPD7298	Approved
0.825	Intermediate Similarity	NPD4773	Phase 2
0.825	Intermediate Similarity	NPD4772	Phase 2
0.8228	Intermediate Similarity	NPD3639	Approved
0.8228	Intermediate Similarity	NPD3640	Phase 3
0.8228	Intermediate Similarity	NPD3641	Approved
0.8125	Intermediate Similarity	NPD4017	Approved
0.8012	Intermediate Similarity	NPD7201	Clinical (unspecified phase)
0.8	Intermediate Similarity	NPD6031	Approved
0.8	Intermediate Similarity	NPD6030	Approved
0.7987	Intermediate Similarity	NPD6028	Clinical (unspecified phase)
0.7987	Intermediate Similarity	NPD6029	Clinical (unspecified phase)
0.7964	Intermediate Similarity	NPD6107	Approved
0.7895	Intermediate Similarity	NPD8156	Discontinued
0.7892	Intermediate Similarity	NPD7833	Phase 2
0.7892	Intermediate Similarity	NPD7832	Clinical (unspecified phase)
0.7892	Intermediate Similarity	NPD7831	Phase 2
0.7881	Intermediate Similarity	NPD2669	Clinical (unspecified phase)
0.7836	Intermediate Similarity	NPD8252	Approved
0.7836	Intermediate Similarity	NPD8251	Approved
0.7836	Intermediate Similarity	NPD8099	Discontinued
0.7824	Intermediate Similarity	NPD4481	Phase 3
0.7811	Intermediate Similarity	NPD3051	Approved
0.7811	Intermediate Similarity	NPD4166	Phase 2
0.7765	Intermediate Similarity	NPD2970	Approved
0.7765	Intermediate Similarity	NPD2969	Approved
0.7747	Intermediate Similarity	NPD4420	Approved
0.7719	Intermediate Similarity	NPD2489	Approved
0.7719	Intermediate Similarity	NPD27	Approved
0.7712	Intermediate Similarity	NPD5718	Phase 2
0.7702	Intermediate Similarity	NPD3124	Discontinued
0.7697	Intermediate Similarity	NPD5752	Clinical (unspecified phase)
0.7688	Intermediate Similarity	NPD5241	Discontinued
0.7688	Intermediate Similarity	NPD5312	Approved
0.7688	Intermediate Similarity	NPD5313	Approved
0.7662	Intermediate Similarity	NPD554	Clinical (unspecified phase)
0.7616	Intermediate Similarity	NPD2898	Approved
0.7605	Intermediate Similarity	NPD6818	Clinical (unspecified phase)
0.7602	Intermediate Similarity	NPD4010	Discontinued
0.7581	Intermediate Similarity	NPD5005	Approved
0.7581	Intermediate Similarity	NPD5006	Approved
0.7571	Intermediate Similarity	NPD7280	Phase 3
0.7571	Intermediate Similarity	NPD7281	Phase 3
0.7528	Intermediate Similarity	NPD8054	Approved
0.7528	Intermediate Similarity	NPD8053	Approved
0.7515	Intermediate Similarity	NPD6788	Approved
0.75	Intermediate Similarity	NPD3110	Approved
0.75	Intermediate Similarity	NPD6071	Discontinued
0.75	Intermediate Similarity	NPD3109	Approved
0.7485	Intermediate Similarity	NPD2420	Approved
0.7485	Intermediate Similarity	NPD2421	Approved
0.7457	Intermediate Similarity	NPD6688	Approved
0.7457	Intermediate Similarity	NPD6687	Approved
0.7456	Intermediate Similarity	NPD2560	Approved
0.7456	Intermediate Similarity	NPD2563	Approved
0.7455	Intermediate Similarity	NPD4727	Phase 1
0.7442	Intermediate Similarity	NPD7802	Discontinued
0.7439	Intermediate Similarity	NPD1754	Clinical (unspecified phase)
0.7405	Intermediate Similarity	NPD2492	Phase 1
0.7403	Intermediate Similarity	NPD7291	Discontinued
0.7396	Intermediate Similarity	NPD2977	Approved
0.7396	Intermediate Similarity	NPD2978	Approved
0.7382	Intermediate Similarity	NPD4859	Phase 1
0.7374	Intermediate Similarity	NPD2971	Approved
0.7374	Intermediate Similarity	NPD2968	Approved
0.7372	Intermediate Similarity	NPD6812	Clinical (unspecified phase)
0.7371	Intermediate Similarity	NPD5602	Clinical (unspecified phase)
0.7362	Intermediate Similarity	NPD5307	Clinical (unspecified phase)
0.7358	Intermediate Similarity	NPD6896	Approved
0.7358	Intermediate Similarity	NPD6895	Approved
0.7353	Intermediate Similarity	NPD5977	Approved
0.7353	Intermediate Similarity	NPD5978	Approved
0.7349	Intermediate Similarity	NPD5976	Discontinued
0.7333	Intermediate Similarity	NPD6853	Approved
0.7333	Intermediate Similarity	NPD6851	Approved
0.7333	Intermediate Similarity	NPD7090	Clinical (unspecified phase)
0.7326	Intermediate Similarity	NPD7400	Phase 3
0.7325	Intermediate Similarity	NPD4474	Approved
0.7325	Intermediate Similarity	NPD4475	Approved
0.7317	Intermediate Similarity	NPD3845	Phase 1
0.7312	Intermediate Similarity	NPD4108	Discontinued
0.731	Intermediate Similarity	NPD4581	Clinical (unspecified phase)
0.7308	Intermediate Similarity	NPD7906	Approved
0.7303	Intermediate Similarity	NPD6297	Approved
0.7293	Intermediate Similarity	NPD5087	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD4577	Approved
0.7278	Intermediate Similarity	NPD4578	Approved
0.7278	Intermediate Similarity	NPD5917	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD7310	Approved
0.7278	Intermediate Similarity	NPD7312	Approved
0.7278	Intermediate Similarity	NPD7311	Approved
0.7278	Intermediate Similarity	NPD7313	Approved
0.7273	Intermediate Similarity	NPD7598	Phase 2
0.7267	Intermediate Similarity	NPD5604	Discontinued
0.7262	Intermediate Similarity	NPD7261	Clinical (unspecified phase)
0.7247	Intermediate Similarity	NPD3885	Approved
0.7238	Intermediate Similarity	NPD7309	Approved
0.7235	Intermediate Similarity	NPD5720	Discontinued
0.7235	Intermediate Similarity	NPD7945	Clinical (unspecified phase)
0.7226	Intermediate Similarity	NPD7247	Discontinued
0.7216	Intermediate Similarity	NPD6365	Clinical (unspecified phase)
0.7208	Intermediate Similarity	NPD7258	Clinical (unspecified phase)
0.7195	Intermediate Similarity	NPD6331	Phase 2
0.7195	Intermediate Similarity	NPD6748	Discontinued
0.7195	Intermediate Similarity	NPD6658	Clinical (unspecified phase)
0.7186	Intermediate Similarity	NPD6090	Discontinued
0.7166	Intermediate Similarity	NPD5582	Discontinued
0.7166	Intermediate Similarity	NPD7667	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD4663	Approved
0.7152	Intermediate Similarity	NPD7294	Phase 1
0.7135	Intermediate Similarity	NPD2488	Approved
0.7135	Intermediate Similarity	NPD2490	Approved
0.7134	Intermediate Similarity	NPD4236	Phase 3
0.7134	Intermediate Similarity	NPD4237	Approved
0.7134	Intermediate Similarity	NPD5177	Phase 3
0.7127	Intermediate Similarity	NPD8453	Clinical (unspecified phase)
0.7124	Intermediate Similarity	NPD3705	Approved
0.712	Intermediate Similarity	NPD7243	Clinical (unspecified phase)
0.712	Intermediate Similarity	NPD3349	Phase 2
0.7108	Intermediate Similarity	NPD2422	Clinical (unspecified phase)
0.7101	Intermediate Similarity	NPD4210	Discontinued
0.71	Intermediate Similarity	NPD3763	Approved
0.7091	Intermediate Similarity	NPD5754	Discontinued
0.7086	Intermediate Similarity	NPD6037	Discontinued
0.7083	Intermediate Similarity	NPD3647	Clinical (unspecified phase)
0.7081	Intermediate Similarity	NPD4579	Clinical (unspecified phase)
0.7076	Intermediate Similarity	NPD7110	Phase 1
0.7076	Intermediate Similarity	NPD7109	Clinical (unspecified phase)
0.7073	Intermediate Similarity	NPD7037	Approved
0.7056	Intermediate Similarity	NPD3815	Phase 1
0.7056	Intermediate Similarity	NPD3816	Phase 1
0.7053	Intermediate Similarity	NPD8095	Phase 1
0.7051	Intermediate Similarity	NPD4098	Discontinued
0.7049	Intermediate Similarity	NPD6618	Phase 2
0.7043	Intermediate Similarity	NPD5525	Clinical (unspecified phase)
0.7039	Intermediate Similarity	NPD4498	Clinical (unspecified phase)
0.7037	Intermediate Similarity	NPD5564	Approved
0.7035	Intermediate Similarity	NPD3383	Approved
0.7035	Intermediate Similarity	NPD3382	Approved
0.7035	Intermediate Similarity	NPD3384	Approved
0.703	Intermediate Similarity	NPD4162	Approved
0.7024	Intermediate Similarity	NPD7019	Approved
0.7024	Intermediate Similarity	NPD7020	Approved
0.7024	Intermediate Similarity	NPD1424	Approved
0.7018	Intermediate Similarity	NPD1337	Clinical (unspecified phase)
0.7017	Intermediate Similarity	NPD6996	Clinical (unspecified phase)
0.7006	Intermediate Similarity	NPD7124	Phase 2
0.7005	Intermediate Similarity	NPD7296	Approved
0.6994	Remote Similarity	NPD1753	Discontinued
0.6989	Remote Similarity	NPD5677	Discontinued
0.6989	Remote Similarity	NPD3408	Clinical (unspecified phase)
0.6982	Remote Similarity	NPD5261	Clinical (unspecified phase)
0.697	Remote Similarity	NPD7045	Clinical (unspecified phase)
0.697	Remote Similarity	NPD7827	Phase 1
0.6963	Remote Similarity	NPD7237	Clinical (unspecified phase)
0.6959	Remote Similarity	NPD4005	Discontinued
0.6951	Remote Similarity	NPD2161	Phase 2
0.6947	Remote Similarity	NPD2973	Approved
0.6947	Remote Similarity	NPD2974	Approved
0.6947	Remote Similarity	NPD2975	Approved
0.6941	Remote Similarity	NPD2122	Discontinued
0.6941	Remote Similarity	NPD6662	Clinical (unspecified phase)
0.694	Remote Similarity	NPD7132	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD7119	Phase 2
0.6931	Remote Similarity	NPD6493	Phase 3
0.6928	Remote Similarity	NPD3060	Approved
0.6927	Remote Similarity	NPD5457	Discontinued
0.6923	Remote Similarity	NPD1669	Approved
0.6923	Remote Similarity	NPD7607	Clinical (unspecified phase)
0.6919	Remote Similarity	NPD6876	Approved
0.6919	Remote Similarity	NPD6875	Approved
0.6909	Remote Similarity	NPD1375	Discontinued
0.6902	Remote Similarity	NPD3534	Clinical (unspecified phase)
0.6899	Remote Similarity	NPD7905	Discontinued
0.6897	Remote Similarity	NPD5772	Approved
0.6897	Remote Similarity	NPD5773	Approved
0.6894	Remote Similarity	NPD3530	Approved
0.6894	Remote Similarity	NPD3531	Approved
0.6894	Remote Similarity	NPD3532	Approved
0.6894	Remote Similarity	NPD2674	Phase 3
0.6886	Remote Similarity	NPD3977	Clinical (unspecified phase)
0.6879	Remote Similarity	NPD6386	Approved
0.6879	Remote Similarity	NPD6385	Approved
0.6875	Remote Similarity	NPD4055	Discovery
0.6868	Remote Similarity	NPD3920	Phase 2
0.6867	Remote Similarity	NPD1372	Clinical (unspecified phase)
0.686	Remote Similarity	NPD6523	Clinical (unspecified phase)
0.6857	Remote Similarity	NPD2358	Clinical (unspecified phase)
0.6847	Remote Similarity	NPD8318	Clinical (unspecified phase)
0.6845	Remote Similarity	NPD3692	Discontinued
0.6842	Remote Similarity	NPD7427	Discontinued
0.6842	Remote Similarity	NPD1914	Approved
0.6839	Remote Similarity	NPD4580	Approved
0.6839	Remote Similarity	NPD7248	Discontinued
0.6836	Remote Similarity	NPD5709	Phase 3
0.6826	Remote Similarity	NPD44	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